Researcher basic information

• 博士（理学）, 総合研究大学院大学（総研大）

• https://researchmap.jp/read0096782?lang=en

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200901001689839406
• https://www.repdev-katsu.jp/index.html

• 00332180

• 200901001689839406

• 分子進化
• 種特異性
• 性ホルモン受容体
• 分化
• 細胞分裂
• 性ホルモン

• Life Science, Developmental biology
• Life Science, Morphology and anatomical structure, 比較内分泌学

• Bachelor's degree program, School of Science
• Master's degree program, Graduate School of Life Science
• Doctoral (PhD) degree program, Graduate School of Life Science

Research activity information

• Comparison of transcriptional activation by corticosteroids of human MR (Ile-180) and haplotype (Val-180).
  Yoshinao Katsu; Jiawen Zhang; Ya Ao; Patricia Donnellan; Michael E Baker
  Biochemical and biophysical research communications, 816, 153689, 153689, 04 Jun. 2026, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal, While the human mineralocorticoid receptor (MR) regulates electrolyte homeostasis through aldosterone activation of the kidney MR, the MR also is highly expressed in the brain, where the MR is activated by cortisol. Here, we report the half-maximal response (EC50) and fold-activation by cortisol, aldosterone and other corticosteroids of human MR rs5522, a haplotype containing valine at codon 180 instead of isoleucine found in wild-type MR (Ile-180). MR rs5522 (Val-180) has been studied for actions in the human brain involving coping with stress and depression. We compared the EC50 and fold-activation by corticosteroids of MR rs5522 and wild-type MR transfected into HEK293 cells with either the TAT3 promoter or the MMTV promoter. Parallel studies investigated the binding of MR antagonists, spironolactone and progesterone, to MR rs5522 to investigate their use as antagonists of MR rs5522. In HEK293 cells with the MMTV promoter, MR rs5522 had a slightly higher EC50 compared to wild-type MR and a similar fold-activation for all corticosteroids. In contrast, in HEK293 cells with the TAT3 promoter, MR rs5522 had a higher EC50 (lower affinity) and fold-activation for cortisol compared to wild-type MR (Ile-180), while compared to wild-type MR, the EC50s of MR rs5522 for aldosterone and corticosterone were slightly lower and fold-activation was higher. Spironolactone and progesterone had similar antagonist activity for MR rs5522 and MR (Ile-180) in the presence of MMTV and TAT3 promoters in HEK293 cells indicating these antagonists are potential regulators of brain MR rs5522 to treat hyperactivity that contributes to chronic fatigue syndrome.
• Transcriptional Activation of Estrogen Receptor-Alpha and Estrogen Receptor-Beta from Elephant Shark (Callorhynchus milii).
  Ya Ao; Haruka Narita; Wataru Takagi; Susumu Hyodo; Michael E Baker; Yoshinao Katsu
  Genes, 17, 3, 17 Mar. 2026, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, BACKGROUND/OBJECTIVES: Humans and other vertebrates contain two estrogen receptors (ERs), ERa and ERb. Among cartilaginous fish (sharks, rays, skates), which are chondrichthyans that evolved about 425 million years ago, only activation by steroids of ERb orthologs has been characterized. To remedy this gap in understanding estrogen signaling in chondrichthyans, we studied estrogen activation of orthologs of human ERa and ERb from elephant shark (Callorhynchus milii). METHODS/RESULTS: Unexpectedly, we found that C. milii contained three estrogen-responsive ERa genes: ERa1 (596 amino acids), ERa2 (600 amino acids), and ERa3 (599 amino acids) with strong sequence similarity to each other. We also found an estrogen-unresponsive gene, ERa4 (561 amino acids), with a 39 amino acid deletion in the DNA-binding domain. An estrogen-responsive ERb ortholog (580 amino acids) was also present in C. milii. The three active C. milii ERas are of similar length to human ERa (595 amino acids); however, C. milii ERb is longer than human ERb (530 amino acids). We studied transcriptional activation of ERa and ERb by estradiol (E2), the main reproductive estrogen in humans. We also studied estrone (E1), the main postmenopausal estrogen, and estriol (E3), which is synthesized during pregnancy. We determined the half-maximal response (EC50) and fold-activation to E2, E1, and E3 of C. milii ERa1, ERa2, ERa3, and ERb. Among these estrogens, E2 had the lowest EC50 for all four ERs. Fold-activation by E2 and E3 was similar for ERa1, ERa2, ERa3, and ERb. CONCLUSIONS: Overall, estrogen activation of C. milii ERa and ERb was similar to that for human ERa and ERb, indicating substantial conservation of the vertebrate ER during the 425 million years since the divergence of cartilaginous fish and humans from a common ancestor.
• Human and zebrafish mineralocorticoid receptors reporter cell assays to assess the activity of chemicals.
  Anna Toso; Abdelhay Boulahtouf; Marina Grimaldi; Audrey Sansaloni; Yoshinao Katsu; Michael E Baker; Aurélie Escande; Clémentine Garoche; Selim Aït-Aïssa; Patrick Balaguer
  iScience, 28, 11, 113764, 113764, 21 Nov. 2025, [Peer-reviewed], [International Magazine]
  English, Scientific journal, The action of environmental chemicals (ECs) on the mineralocorticoid receptor (MR) has been suggested to impair physiological processes regulated by this nuclear receptor. However, it remains understudied both as a target of ECs and with respect to potential species-specific differences. In this regard, we have developed reporter cell lines to identify the response to different steroids, ECs, and urban wastewater (WW) sample extracts of human MR (hMR) and zebrafish MR (zfMR). Most of the steroids had a higher efficacy on zfMR than hMR, while the ECs were antagonists to both hMR and zfMR, with a lower potency on the latter. Interestingly, WW sample extracts revealed the presence of MR activity with a greater activity on zfMR compared to hMR, suggesting the presence of steroids in WW. These screening tools have proven to be powerful tools for characterizing the interaction of chemicals with MRs and revealing their presence in environmental samples.
• Functional characterizations of thermosensitive TRPV channels from Holocephalan elephant shark, Callorhinchus milii, illuminate the ancestral thermosensory system in vertebrates.
  Sumika Otake; Shigeru Saito; Xiaozhi Lin; Claire T Saito; Satomi Kohno; Wataru Takagi; Susumu Hyodo; Makoto Tominaga; Yoshinao Katsu
  The Journal of experimental biology, 07 Feb. 2025, [Peer-reviewed], [Corresponding author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, Homeostasis and survival of various animal species have been affected by changes in environmental temperature, causing animals to evolve physiological systems for sensing ambient and body temperature. Temperature-sensitive transient receptor potential (TRP) channels have multimodal properties that are activated by physical stimuli such as temperature, as well as by various chemical substances. Our goal is to understand the diversity of the vertebrate thermosensory system by characterizing the temperature-sensitive TRPV channels of the elephant shark, which belongs to the holocephali of the cartilaginous fishes. Since elephant sharks are basal jawed vertebrates, analysis of elephant shark TRPs is critical to understanding the evolution of thermosensory systems in vertebrate lineages. We found that temperature stimulation activated elephant shark TRPVs in an electrophysiological analysis similar to the mammalian orthologue. The thermal activation threshold of elephant shark TRPV1 (31°C) was similar to the thresholds reported for several other fish species, but was much lower than that of mammalian orthologs. Strikingly, the elephant shark TRPV4 was a cooling-activated channel with a threshold of 20°C, whereas, in several tetrapods, it is activated by warmth. These results suggest that the temperature sensitivity of TRPV4 has changed in vertebrate evolutionary lineages. Furthermore, we also found the elephant shark possesses heat-evoked TRPV3, which has a threshold of 42°C, which is absent in more derived teleost fishes. Taken together, our findings elucidate that the vertebrate-type thermosensory system has already emerged in the common ancestor of jawed vertebrates, although their temperature sensing ranges were different from those of mammals.
• Lysine-Cysteine-Serine-Tryptophan inserted into the DNA-binding domain of human mineralocorticoid receptor increases transcriptional activation by aldosterone.
  Yoshinao Katsu; Jiawen Zhang; Michael E Baker
  The Journal of steroid biochemistry and molecular biology, 243, 106548, 106548, Oct. 2024, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, Due to alternative splicing in an ancestral DNA-binding domain (DBD) of the mineralocorticoid receptor (MR), humans contain two almost identical MR transcripts with either 984 amino acids (MR-984) or 988 amino acids (MR-988), in which their DBDs differ by only four amino acids, Lys,Cys,Ser,Trp (KCSW). Human MRs also contain mutations at two sites, codons 180 and 241, in the amino terminal domain (NTD). Together, there are five distinct full-length human MR genes in GenBank. Human MR-984, which was cloned in 1987, has been extensively studied. Human MR-988, cloned in 1995, contains KCSW in its DBD. Neither this human MR-988 nor the other human MR-988 genes have been studied for their response to aldosterone and other corticosteroids. Here, we report that transcriptional activation of human MR-988 by aldosterone is increased by about 50 % compared to activation of human MR-984 in HEK293 cells transfected with the TAT3 promoter, while the half-maximal response (EC50) is similar for aldosterone activation of MR-984 and MR-988. Transcriptional activation of human MR also depends on the amino acids at codons 180 and 241. Interestingly, in HEK293 cells transfected with the MMTV promoter, transcriptional activation by aldosterone of human MR-988 is similar to activation of human MR-984, indicating that the promoter has a role in the regulation of the response of human MR-988 to aldosterone. The physiological responses to aldosterone and other corticosteroids in humans with MR genes containing KCSW and with differences at codons 180 and 241 in the NTD warrant investigation.
• Novel Evolution of Mineralocorticoid Receptor in Humans Compared to Chimpanzees, Gorillas, and Orangutans.
  Yoshinao Katsu; Jiawen Zhang; Michael E Baker
  Genes, 15, 6, 12 Jun. 2024, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, We identified five distinct full-length human mineralocorticoid receptor (MR) genes containing either 984 amino acids (MR-984) or 988 amino acids (MR-988), which can be distinguished by the presence or absence of Lys, Cys, Ser, and Trp (KCSW) in their DNA-binding domain (DBD) and mutations at codons 180 and 241 in their amino-terminal domain (NTD). Two human MR-KCSW genes contain either (Val-180, Val-241) or (Ile-180, Val-241) in their NTD, and three human MR-984 genes contain either (Ile-180, Ala-241), (Val-180, Val-241), or (Ile-180, Val-241). Human MR-KCSW with (Ile-180, Ala-241) has not been cloned. In contrast, chimpanzees contain four MRs: two MR-988s with KCSW in their DBD, or two MR-984s without KCSW in their DBD. Chimpanzee MRs only contain (Ile180, Val-241) in their NTD. A chimpanzee MR with either (Val-180, Val-241) or (Ile-180, Ala-241) in the NTD has not been cloned. Gorillas and orangutans each contain one MR-988 with KCSW in the DBD and one MR-984 without KCSW, and these MRs only contain (Ile-180, Val-241) in their NTD. A gorilla MR or orangutan MR with either (Val-180, Val-241) or (Ile-180, Ala-241) in the NTD has not been cloned. Together, these data suggest that human MRs with (Val-180, Val-241) or (Ile-180, Ala-241) in the NTD evolved after humans and chimpanzees diverged from their common ancestor. Considering the multiple functions in human development of the MR in kidney, brain, heart, skin, and lungs, as well as MR activity in interaction with the glucocorticoid receptor, we suggest that the evolution of human MRs that are absent in chimpanzees may have been important in the evolution of humans from chimpanzees. Investigation of the physiological responses to corticosteroids mediated by the MR in humans, chimpanzees, gorillas, and orangutans may provide insights into the evolution of humans and their closest relatives.
• N-terminal domain influences steroid activation of the Atlantic sea lamprey corticoid receptor.
  Yoshinao Katsu; Xiaozhi Lin; Ruigeng Ji; Ze Chen; Yui Kamisaka; Koto Bamba; Michael E Baker
  The Journal of steroid biochemistry and molecular biology, 228, 106249, 106249, Apr. 2023, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, Lampreys are jawless fish that evolved about 550 million years ago at the base of the vertebrate line. Modern lampreys contain a corticoid receptor (CR), the common ancestor of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which first appear in cartilaginous fish, such as sharks. Until recently, 344 amino acids at the amino terminus of adult lamprey CR were not present in the lamprey CR sequence in GenBank. A search of the recently sequenced lamprey germline genome identified two CR sequences, CR1 and CR2, containing the 344 previously un-identified amino acids. CR1 also contains a novel four amino acid insertion in the DNA-binding domain (DBD). We studied corticosteroid and progesterone activation of CR1 and CR2 and found their strongest response was to 11-deoxycorticosterone and 11-deoxycortisol, the two circulating corticosteroids in lamprey. Based on steroid specificity, both CRs are close to elephant shark MR and distant from elephant shark GR. HEK293 cells that were transfected with full-length CR1 or CR2 and the MMTV promoter have about 3-fold higher steroid-mediated activation compared to HEK293 cells transfected with these CRs and the TAT3 promoter. Deletion of the amino-terminal domain (NTD) of lamprey CR1 and CR2 to form truncated CRs decreased transcriptional activation by about 70% in HEK293 cells that were transfected with MMTV, but increased transcription by about 6-fold in cells transfected with TAT3. This indicated that the promoter has an important effect on NTD regulation of transcriptional activation of the CR by steroids. Our results also indicate that the entire lamprey CR sequence is needed for an accurate determination of steroid-mediated transcription.
• Reduced steroid activation of elephant shark GR and MR after inserting four amino acids from the DNA-binding domain of lamprey corticoid receptor-1.
  Yoshinao Katsu; Jiawen Zhang; Michael E Baker
  PloS one, 18, 8, e0290159, 2023, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, Atlantic sea lamprey contains two corticoid receptors (CRs), CR1 and CR2, that have identical amino acid sequences, except for a four amino acid insert (Thr-Arg-Gln-Gly) in the CR1 DNA-binding domain (DBD). Steroids are stronger transcriptional activators of CR2 than of CR1 suggesting that the insert reduces the transcriptional response of lamprey CR1 to steroids. The DBD in elephant shark mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), which are descended from a CR, lack these four amino acids, suggesting that a CR2 is their common ancestor. To determine if, similar to lamprey CR1, the presence of this insert in elephant shark MR and GR decreases transcriptional activation by corticosteroids, we inserted these four CR1-specific residues into the DBD of elephant shark MR and GR. Compared to steroid activation of wild-type elephant shark MR and GR, cortisol, corticosterone, aldosterone, 11-deoxycorticosterone and 11-deoxycortisol had lower transcriptional activation of these mutant MR and GR receptors, indicating that the absence of this four-residue segment in the DBD in wild-type elephant shark MR and GR increases transcriptional activation by corticosteroids.
• Regulation by Progestins, Corticosteroids, and RU486 of Transcriptional Activation of Elephant Shark and Human Progesterone Receptors: An Evolutionary Perspective.
  Xiaozhi Lin; Wataru Takagi; Susumu Hyodo; Shigeho Ijiri; Yoshinao Katsu; Michael E Baker
  ACS pharmacology & translational science, 5, 2, 52, 61, 11 Feb. 2022, [Peer-reviewed], [Corresponding author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, We investigated progestin and corticosteroid activation of the progesterone receptor (PR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates. Comparison with the human PR provides insights into the evolution of steroid activation of the human PR. At 1 nM steroid, the elephant shark PR is activated by progesterone, 17-hydroxy-progesterone, 20β-hydroxy-progesterone, 11-deoxycorticosterone (21-hydroxyprogesterone), and 11-deoxycortisol. The human PR, in comparison, is activated at 1 nM steroid, only by progesterone and 11-deoxycorticosterone, indicating increased progestin and corticosteroid specificity during the evolution of the human PR. RU486, an important clinical antagonist of the human PR, did not inhibit progesterone activation of the elephant shark PR. Cys-528 in the elephant shark PR corresponds to Gly-722 in the human PR, which is essential for RU486 inhibition of the human PR. Confirming the importance of Cys-528 in the elephant shark PR, RU486 inhibited progesterone activation of the Cys528Gly mutant PR. To investigate the physiological relevance of Gly-722 in the human PR and Cys-528 in the elephant shark PR, we studied steroid activation of the Gly722Cys human PR and Cys528Gly elephant shark PR. Compared to the wild-type human PR, there was an increase in the activation of human Gly722Cys PR by11-deoxycortisol and a decrease in activation by corticosterone, which may have been important in selection for the mutation corresponding to the human glycine-722 PR that first evolved in the platypus PR, a basal mammal.
• Cloning of nine glucocorticoid receptor isoforms from the slender African lungfish (Protopterus dolloi).
  Yoshinao Katsu; Shin Oana; Xiaozhi Lin; Susumu Hyodo; Laurent Bianchetti; Michael E Baker
  PloS one, 17, 8, e0272219, 2022, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, We wanted to clone the glucocorticoid receptor (GR) from slender African lungfish (Protopterus dolloi) for comparison to the P. dolloi mineralocorticoid receptor (MR), which we had cloned and were characterizing, as well as for comparison to the GRs from humans, elephant shark and zebrafish. However, although sequencing of the genome of the Australian lungfish (Neoceratodus forsteri), as well as, that of the West African lungfish (Protopterus annectens) were reported in the first three months of 2021, we could not retrieve a GR sequence with a BLAST search of GenBank, when we submitted our research for publication in July 2021. Moreover, we were unsuccessful in cloning the GR from slender African lungfish using a cDNA from the ovary of P. dolloi and PCR primers that had successfully cloned a GR from elephant shark, Xenopus and gar GRs. On October 21, 2021 the nucleotide sequence of West African lungfish (P. annectens) GR was deposited in GenBank. We used this GR sequence to construct PCR primers that successfully cloned the GR from the slender spotted lungfish. Here, we report the sequences of nine P. dolloi GR isoforms and explain the basis for the previous failure to clone a GR from slender African lungfish using PCR primers that cloned the GR from elephant shark, Xenopus and gar. Studies are underway to determine corticosteroid activation of these slender African lungfish GRs.
• Aldosterone and dexamethasone activate African lungfish mineralocorticoid receptor: Increased activation after removal of the amino-terminal domain
  Yoshinao Katsu; Shin Oana; Xiaozhi Lin; Susumu Hyodo; Michael E. Baker
  JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 215, Jan. 2022, [Peer-reviewed], [Lead author], ［Internationally co-authored］
  English, Scientific journal
• Diversification of mineralocorticoid receptor genes in a subterranean rodent, the naked mole-rat
  Kaori Oka; Hidemasa Bono; Asato Kuroiwa; Shusuke Fujioka; Atsushi Shimizu; Yoshinao Katsu; Kyoko Miura
  Journal of Molecular Endocrinology, 66, 4, 299, 311, Bioscientifica, Apr. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Naked mole-rats (Heterocephalus glaber) inhabit subterranean burrows in savannas and are thus unable to access free water. To identify their mechanism of osmoregulation in xeric environments, we molecularly cloned and analyzed the mineralocorticoid receptor (MR) gene, required for hormone-dependent regulation of genes contributing to body fluid homeostasis. Most vertebrates harbor a single MR homolog. In contrast, we discovered that MR is duplicated in naked mole-rats. The amino acid sequence of naked mole-rat MR1 is 90% identical to its mouse ortholog, and MR1 is abundantly expressed in the kidney and the nervous system. MR2 encodes a truncated protein lacking DNA- and ligand-binding domains of MR1 and is expressed in diverse tissues. Although MR2 did not directly transactivate gene expression, it increased corticosteroid-dependent transcriptional activity of MR1. Our results suggest that MR2 might function as a novel regulator of MR1 activity to fine-tune MR signaling in naked mole-rats.
• N-terminal domain regulates steroid activation of elephant shark glucocorticoid and mineralocorticoid receptors.
  Yoshinao Katsu; Islam M D Shariful; Xiaozhi Lin; Wataru Takagi; Hiroshi Urushitani; Satomi Kohno; Susumu Hyodo; Michael E Baker
  The Journal of steroid biochemistry and molecular biology, 210, 105845, 105845, 27 Feb. 2021, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, Orthologs of human glucocorticoid receptor (GR) and human mineralocorticoid receptor (MR) first appear in cartilaginous fishes. Subsequently, the MR and GR diverged to respond to different steroids: the MR to aldosterone and the GR to cortisol and corticosterone. We report that cortisol, corticosterone and aldosterone activate full-length elephant shark GR, and progesterone, which activates elephant shark MR, does not activate elephant shark GR. However, progesterone inhibits steroid binding to elephant shark GR, but not to human GR. Together, this indicates partial functional divergence of elephant shark GR from the MR. Deletion of the N-terminal domain (NTD) from elephant shark GR (truncated GR) reduced the response to corticosteroids, while truncated and full-length elephant shark MR had similar responses to corticosteroids. Swapping of NTDs of elephant shark GR and MR yielded an elephant shark MR chimera with full-length GR-like increased activation by corticosteroids and progesterone compared to full-length elephant shark MR. Elephant shark MR NTD fused to GR DBD + LBD had similar activation as full-length MR, indicating that the MR NTD lacked GR-like NTD activity. We propose that NTD activation of human GR evolved early in GR divergence from the MR.
• Progesterone: An enigmatic ligand for the mineralocorticoid receptor.
  Michael E Baker; Yoshinao Katsu
  Biochemical pharmacology, 177, 113976, 113976, Jul. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, The progesterone receptor (PR) mediates progesterone regulation of female reproductive physiology, as well as gene transcription in non-reproductive tissues, such as brain, bone, lung and vasculature, in both women and men. An unusual property of progesterone is its high affinity for the mineralocorticoid receptor (MR), which regulates electrolyte transport in the kidney in humans and other terrestrial vertebrates. In humans, rats, alligators and frogs, progesterone antagonizes activation of the MR by aldosterone, the physiological mineralocorticoid in terrestrial vertebrates. In contrast, in elephant shark, ray-finned fishes and chickens, progesterone activates the MR. Interestingly, cartilaginous fishes and ray-finned fishes do not synthesize aldosterone, raising the question of which steroid(s) activate the MR in cartilaginous fishes and ray-finned fishes. The simpler synthesis of progesterone, compared to cortisol and other corticosteroids, makes progesterone a candidate physiological activator of the MR in elephant sharks and ray-finned fishes. Elephant shark and ray-finned fish MRs are expressed in diverse tissues, including heart, brain and lung, as well as, ovary and testis, two reproductive tissues that are targets for progesterone, which together suggests a multi-faceted physiological role for progesterone activation of the MR in elephant shark and ray-finned fish. The functional consequences of progesterone as an antagonist of some terrestrial vertebrate MRs and as an agonist of fish and chicken MRs are not fully understood. The physiological activities of progesterone through binding to vertebrate MRs merits further investigation.
• Oil dispersant Corexit 9500 is weakly estrogenic, but does not skew the sex ratio in Alligator mississippiensis.
  Nicole A McNabb; Melissa C Bernhard; Arnold Brunell; Russell H Lowers; Yoshinao Katsu; Demetri D Spyropoulos; Satomi Kohno
  Journal of applied toxicology : JAT, 40, 2, 245, 256, Feb. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, During the Deepwater Horizon oil spill, vast quantities of a chemical dispersant Corexit 9500 were applied in remediation efforts. In addition to the acute toxicity, it is essential to evaluate Corexit further with a broader scope of long-term sublethal endocrine endpoints. The American alligator (Alligator mississippiensis) is an excellent organism for such an endeavor. It exhibits temperature-dependent sex determination, in which egg incubation temperatures during a thermosensitive period (TSP) in embryonic development determine the sex of embryos. Estrogen signals play a critical role in this process. For example, a single exposure to exogenous estrogen during the TSP overrides the effects of temperature and leads to skewed sex ratios. At a concentration of 100 ppm, Corexit significantly induced transcriptional activity of both alligator nuclear estrogen receptors 1 and 2 in vitro in reporter gene assays. To investigate the estrogenic effects of Corexit on gonadal development, alligator eggs were exposed to Corexit at environmentally relevant concentrations (0.25, 2.5 and 25 ppm) before the TSP in ovo. Exposure to Corexit at 0.25 and 25 ppm significantly delayed hatching and growth. Corexit exposure at any treatment level did not affect sex ratios or testicular mRNA abundance as measured at 1-week post-hatching, suggesting that the combination of Corexit components did not synergize enough to induce ovarian development in ovo. These results point to a need for further investigations on individual and combined components of Corexit to understand better their long-term effects on the development and reproductive health of alligators and other coastal aquatic wildlife.
• Transcriptional activation of elephant shark mineralocorticoid receptor by corticosteroids, progesterone, and spironolactone.
  Yoshinao Katsu; Satomi Kohno; Kaori Oka; Xiaozhi Lin; Sumika Otake; Nisha E Pillai; Wataru Takagi; Susumu Hyodo; Byrappa Venkatesh; Michael E Baker
  Science signaling, 12, 584, 04 Jun. 2019, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
  English, Scientific journal, The mineralocorticoid receptor (MR) is a nuclear receptor and part of a large and diverse family of transcription factors that also includes receptors for glucocorticoids, progesterone, androgens, and estrogens. The corticosteroid aldosterone is the physiological activator of the MR in humans and other terrestrial vertebrates; however, its activator is not known in cartilaginous fish, the oldest group of extant jawed vertebrates. Here, we analyzed the ability of corticosteroids and progesterone to activate the full-length MR from the elephant shark (Callorhinchus milii). On the basis of their measured activities, aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone, and 19-norprogesterone are potential physiological mineralocorticoids. However, aldosterone, the physiological mineralocorticoid in humans and other terrestrial vertebrates, is not found in cartilaginous or ray-finned fish. Although progesterone activates MRs in ray-finned fish, progesterone does not activate MRs in humans, amphibians, or alligator, suggesting that during the transition to terrestrial vertebrates, progesterone lost the ability to activate the MR. Both elephant shark MR and human MR are expressed in the brain, heart, ovary, testis, and other nonepithelial tissues, suggesting that MR expression in diverse tissues evolved in the common ancestor of jawed vertebrates. Our data suggest that 19-norprogesterone- and progesterone-activated MR may have unappreciated functions in reproductive physiology.
• Evolution of the Mineralocorticoid Receptor.
  Baker ME; Katsu Y
  Vitamins and hormones, 109, 17, 36, 2019, [Peer-reviewed], [Last author, Corresponding author]
  Scientific journal
• Functional distinctions associated with the diversity of sex steroid hormone receptors ESR and AR.
  Yukiko Ogino; Saki Tohyama; Satomi Kohno; Kenji Toyota; Gen Yamada; Ryohei Yatsu; Tohru Kobayashi; Norihisa Tatarazako; Tomomi Sato; Hajime Matsubara; Anke Lange; Charles R Tyler; Yoshinao Katsu; Taisen Iguchi; Shinichi Miyagawa
  The Journal of steroid biochemistry and molecular biology, 184, 38, 46, Nov. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Sex steroid hormones including estrogens and androgens play fundamental roles in regulating reproductive activities and they act through estrogen and androgen receptors (ESR and AR). These steroid receptors have evolved from a common ancestor in association with several gene duplications. In most vertebrates, this has resulted in two ESR subtypes (ESR1 and ESR2) and one AR, whereas in teleost fish there are at least three ESRs (ESR1, ESR2a and ESR2b) and two ARs (ARα and ARβ) due to a lineage-specific whole genome duplication. Functional distinctions have been suggested among these receptors, but to date their roles have only been characterized in a limited number of species. Sexual differentiation and the development of reproductive organs are indispensable for all animal species and in vertebrates these events depend on the action of sex steroid hormones. Here we review the recent progress in understanding of the functions of the ESRs and ARs in the development and expression of sexually dimorphic characteristics associated with steroid hormone signaling in vertebrates, with representative fish, amphibians, reptiles, birds and mammals.
• Evolution of human, chicken, alligator, frog, and zebrafish mineralocorticoid receptors: Allosteric influence on steroid specificity.
  Katsu Y; Oka K; Baker ME
  Science signaling, 11, 537, Jul. 2018, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
  English, Scientific journal, Although multiple steroid ligands of the glucocorticoid, mineralocorticoid, and progestin families bind to and regulate the activity of mineralocorticoid receptors (MRs), the responses to these ligands differ across species. To understand how the different domains of MRs contribute to the ligand-induced activation or inhibition of MR activity, we studied the response to eight steroids (aldosterone, 11-deoxycorticosterone, 11-deoxycortisol, cortisol, corticosterone, progesterone, 19-norprogesterone, and spironolactone) of human, chicken, alligator, frog, and zebrafish full-length MRs and truncated MRs, which lacked the N-terminal domain (NTD) and DNA binding domain (DBD). Compared to full-length MRs, some truncated MRs were not activated by the steroids, and others required higher steroid concentrations for activation. Progesterone, 19-norprogesterone, and spironolactone did not activate full-length or truncated human, alligator, or frog MRs. However, at 10 nM, these steroids activated full-length chicken and zebrafish MRs, whereas at 100 nM, these steroids had little activity for truncated chicken MRs, but they retained activity for truncated zebrafish MRs. This suggests that regulation of the activation of the chicken MR by progestin resides in the NTD-DBD and that of the zebrafish MR resides in the hinge-LBD. Zebrafish and chicken MRs contain a serine corresponding to Ser810 in human MR, which is required for the antagonist activity of progesterone for human MR, suggesting a previously uncharacterized mechanism of regulation of progestin activation of chicken and zebrafish MRs. These findings suggest that progesterone may be a physiological activator of chicken and zebrafish MRs.
• Characterization and comparison of transcriptional activities of the retinoid X receptors by various organotin compounds in three prosobranch gastropods; Thais clavigera, Nucella lapillus and Babylonia japonica
  Hiroshi Urushitani; Yoshinao Katsu; Hiroyuki Kagechika; Ana C.A. Sousa; Carlos M. Barroso; Yasuhiko Ohta; Hiroaki Shiraishi; Taisen Iguchi; Toshihiro Horiguchi
  Aquatic Toxicology, 199, 103, 115, Elsevier B.V., 01 Jun. 2018, [Peer-reviewed]
  English, Scientific journal
• Divergent responsiveness of two isoforms of the estrogen receptor to mixtures of contaminants of emerging concern in four vertebrates
  Satomi Kohno; Yoshinao Katsu; Nicholas Cipoletti; Lina C. Wang; Zachary G. Jorgenson; Shinichi Miyagawa; Heiko L. Schoenfuss
  Journal of Applied Toxicology, 38, 5, 705, 713, John Wiley and Sons Ltd, 01 May 2018, [Peer-reviewed]
  English, Scientific journal
• Progesterone activation of zebrafish mineralocorticoid receptor may influence growth of some transplanted tumors
  Yoshinao Katsu; Michael E. Baker
  Proceedings of the National Academy of Sciences of the United States of America, 115, 13, E2908, E2909, National Academy of Sciences, 27 Mar. 2018, [Peer-reviewed], [Lead author, Corresponding author]
  English, Scientific journal
• Feminizing effects of exposure to Corexit-enhanced water-accommodated fraction of crude oil in vitro on sex determination in Alligator mississippiensis.
  Williams CE; McNabb NA; Brunell A; Lowers RH; Katsu Y; Spyropoulos DD; Kohno S
  General and comparative endocrinology, Dec. 2017, [Peer-reviewed]
• Evolution of the mineralocorticoid receptor: sequence, structure and function
  Michael E. Baker; Yoshinao Katsu
  JOURNAL OF ENDOCRINOLOGY, 234, 1, T1, T16, Jul. 2017, [Peer-reviewed]
  English, Scientific journal
• Molecular cloning and characterization of hagfish estrogen receptors
  Osamu Nishimiya; Yoshinao Katsu; Hiroyuki Inagawa; Naoshi Hiramatsu; Takashi Todo; Akihiko Hara
  JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 165, Pt B, 190, 201, Jan. 2017, [Peer-reviewed]
  English, Scientific journal
• Characterization of evolutionary trend in squamate estrogen receptor sensitivity
  Ryohei Yatsu; Yoshinao Katsu; Satomi Kohno; Takeshi Mizutani; Yukiko Ogino; Yasuhiko Ohta; Jan Myburgh; Johannes H. van Wyk; Louis J. Guillette; Shinichi Miyagawa; Taisen Iguchi
  GENERAL AND COMPARATIVE ENDOCRINOLOGY, 238, 88, 95, Nov. 2016, [Peer-reviewed]
  English, Scientific journal
• Molecular cloning and characterization of the aryl hydrocarbon receptors and aryl hydrocarbon receptor nuclear translocators in the American alligator
  Kaori Oka; Satomi Kohno; Yasuhiko Ohta; Louis J. Guillette; Taisen Iguchi; Yoshinao Katsu
  GENERAL AND COMPARATIVE ENDOCRINOLOGY, 238, 13, 22, Nov. 2016, [Peer-reviewed]
  English, Scientific journal
• Corticosteroid and progesterone transactivation of mineralocorticoid receptors from Amur sturgeon and tropical gar
  Akira Sugimoto; Kaori Oka; Rui Sato; Shinji Adachi; Michael E. Baker; Yoshinao Katsu
  BIOCHEMICAL JOURNAL, 473, 20, 3655, 3665, Oct. 2016, [Peer-reviewed]
  English, Scientific journal
• Evolution of corticosteroid specificity for human, chicken, alligator and frog glucocorticoid receptors
  Yoshinao Katsu; Satomi Kohno; Kaori Oka; Michael E. Baker
  STEROIDS, 113, 38, 45, Sep. 2016, [Peer-reviewed]
  English, Scientific journal
• A second estrogen receptor from Japanese lamprey (Lethenteron japonicum) does not have activities for estrogen binding and transcription
  Yoshinao Katsu; Paul A. Cziko; Charlie Chandsawangbhuwana; Joseph W. Thornton; Rui Sato; Koari Oka; Yoshio Takei; Michael E. Baker; Taisen Iguchi
  GENERAL AND COMPARATIVE ENDOCRINOLOGY, 236, 105, 114, Sep. 2016, [Peer-reviewed]
  English, Scientific journal
• TRPV4 associates environmental temperature and sex determination in the American alligator
  Ryohei Yatsu; Shinichi Miyagawa; Satomi Kohno; Shigeru Saito; Russell H. Lowers; Yukiko Ogino; Naomi Fukuta; Yoshinao Katsu; Yasuhiko Ohta; Makoto Tominaga; Louis J. Guillette; Taisen Iguchi
  SCIENTIFIC REPORTS, 5, 18581, Dec. 2015, [Peer-reviewed]
  English, Scientific journal
• Allosteric role of the amino-terminal A/B domain on corticosteroid transactivation of gar and human glucocorticoid receptors
  Kaori Oka; Andree Hoang; Daijiro Okada; Taisen Iguchi; Michael E. Baker; Yoshinao Katsu
  JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 154, 112, 119, Nov. 2015, [Peer-reviewed]
  English, Scientific journal
• Identification and Characterization of the Androgen Receptor From the American Alligator, Alligator mississippiensis
  Shinichi Miyagawa; Ryohei Yatsu; Satomi Kohno; Brenna M. Doheny; Yukiko Ogino; Hiroshi Ishibashi; Yoshinao Katsu; Yasuhiko Ohta; Louis J. Guillette; Taisen Iguchi
  ENDOCRINOLOGY, 156, 8, 2795, 2806, Aug. 2015, [Peer-reviewed]
  English, Scientific journal
• Understanding the Molecular Basis for Differences in Responses of Fish Estrogen Receptor Subtypes to Environmental Estrogens
  Saki Tohyama; Shinichi Miyagawa; Anke Lange; Yukiko Ogino; Takeshi Mizutani; Norihisa Tatarazako; Yoshinao Katsu; Masaru Ihara; Hiroaki Tanaka; Hiroshi Ishibashi; Tohru Kobayashi; Charles R. Tyler; Taisen Iguchi
  ENVIRONMENTAL SCIENCE & TECHNOLOGY, 49, 12, 7439, 7447, Jun. 2015, [Peer-reviewed]
  English, Scientific journal
• Molecular Cloning and Characterization of Anti-Mullerian Hormone (AMH) from the Japanese Wrinkled Frog, Rana rugosa
  Maho Kodama; Mari Suda; Daiki Sakamoto; Takehiro Iwasaki; Yasuki Matsuo; Yoshinobu Uno; Yoichi Matsuda; Yoriko Nakamura; Shun Maekawa; Yoshinao Katsu; Masahisa Nakamura
  ENDOCRINOLOGY, 156, 5, 1914, 1923, May 2015, [Peer-reviewed]
  English, Scientific journal
• Estrogen Receptor 1 (ESR1; ER alpha), not ESR2 (ER beta), Modulates Estrogen-Induced Sex Reversal in the American Alligator, a Species With Temperature-Dependent Sex Determination
  Satomi Kohno; Melissa C. Bernhard; Yoshinao Katsu; Jianguo Zhu; Teresa A. Bryan; Brenna M. Doheny; Taisen Iguchi; Louis J. Guillette
  ENDOCRINOLOGY, 156, 5, 1887, 1899, May 2015, [Peer-reviewed]
  English, Scientific journal
• Luteinizing Hormone-Induced Expression of Ptger4b, a Prostaglandin E-2 Receptor Indispensable for Ovulation of the Medaka Oryzias latipes, Is Regulated by a Genomic Mechanism Involving Nuclear Progestin Receptor
  Akane Hagiwara; Katsueki Ogiwara; Yoshinao Katsu; Takayuki Takahashi
  BIOLOGY OF REPRODUCTION, 90, 6, Jun. 2014, [Peer-reviewed]
  English, Scientific journal
• Differing Species Responsiveness of Estrogenic Contaminants in Fish Is Conferred by the Ligand Binding Domain of the Estrogen Receptor
  Shinichi Miyagawa; Anke Lange; Ikumi Hirakawa; Saki Tohyama; Yukiko Ogino; Takeshi Mizutani; Yoshihiro Kagami; Teruhiko Kusano; Masaru Ihara; Hiroaki Tanaka; Norihisa Tatarazako; Yasuhiko Ohta; Yoshinao Katsu; Charles R. Tyler; Taisen Iguchi
  ENVIRONMENTAL SCIENCE & TECHNOLOGY, 48, 9, 5254, 5263, May 2014, [Peer-reviewed]
  English, Scientific journal
• Possible involvement of insulin-like growth factor 2 mRNA-binding protein 3 in zebrafish oocyte maturation as a novel cyclin B1 mRNA-binding protein that represses the translation in immature oocytes
  Kazuki Takahashi; Tomoya Kotani; Yoshinao Katsu; Masakane Yamashita
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 448, 1, 22, 27, May 2014, [Peer-reviewed]
  English, Scientific journal
• Nuclear progesterone receptor is involved in the LH-induced expression of Ptger4b, a prostaglandin E-2 receptor indispensable for ovulation of the medaka
  A. Hagiwara; K. Ogiwar; Y. Katsu; T. Takahashi
  PROCEEDINGS OF THE 17TH INTERNATIONAL CONGRESS OF COMPARATIVE ENDOCRINOLOGY (ICCE 2013), 29, 34, 2014, [Peer-reviewed]
  English, International conference proceedings
• Cloning and characterization of the retinoic acid receptor-like protein in the rock shell, Thais clavigera
  Hiroshi Urushitani; Yoshinao Katsu; Yasuhiko Ohta; Hiroaki Shiraishi; Taisen Iguchi; Toshihiro Horiguchi
  Aquatic Toxicology, 142-143, 403, 412, 15 Oct. 2013, [Peer-reviewed]
  English, Scientific journal
• Establishment of transactivation assay systems using fish, amphibian, reptilian and human thyroid hormone receptors
  Tomohiro Oka; Naoko Mitsui-Watanabe; Norihisa Tatarazako; Yuta Onishi; Yoshinao Katsu; Shinichi Miyagawa; Yukiko Ogino; Ryohei Yatsu; Satomi Kohno; Minoru Takase; Yukio Kawashima; Yasuhiko Ohta; Yasunobu Aoki; Louis J. Guillette; Taisen Iguchi
  Journal of Applied Toxicology, 33, 9, 991, 1000, John Wiley and Sons Ltd, 01 Sep. 2013, [Peer-reviewed]
  English, Scientific journal
• Cloning, expression and functional characterization of carp, Cyprinus carpio, estrogen receptors and their differential activations by estrogens
  Yoshinao Katsu; Anke Lange; Shinichi Miyagawa; Hiroshi Urushitani; Norishisa Tatarazako; Yukio Kawashima; Charles R. Tyler; Taisen Iguchi
  JOURNAL OF APPLIED TOXICOLOGY, 33, 1, 41, 49, Jan. 2013, [Peer-reviewed]
  English, Scientific journal
• Molecular cloning and characterization of the corticoid receptors from the American alligator
  Kaori Oka; Satomi Kohno; Hiroshi Urushitani; Louis J. Guillette; Yasuhiko Ohta; Taisen Iguchi; Yoshinao Katsu
  MOLECULAR AND CELLULAR ENDOCRINOLOGY, 365, 2, 153, 161, Jan. 2013, [Peer-reviewed]
  English, Scientific journal
• p21 and Notch Signalings in the Persistently Altered Vagina Induced by Neonatal Diethylstilbestrol Exposure in Mice
  Takeshi Nakamura; Shinichi Miyagawa; Yoshinao Katsu; Takeshi Mizutani; Tomomi Sato; Takashi Takeuchi; Taisen Iguchi; Yasuhiko Ohta
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 74, 12, 1589, 1595, Dec. 2012, [Peer-reviewed]
  English, Scientific journal
• Sequential Changes in the Expression of Wnt- and Notch-related Genes in the Vagina and Uterus of Ovariectomized Mice after Estrogen Exposure
  Takeshi Nakamura; Shinichi Miyagawa; Yoshinao Katsu; Tomomi Sato; Taisen Iguchi; Yasuhiko Ohta
  IN VIVO, 26, 6, 899, 906, Nov. 2012, [Peer-reviewed]
  English, Scientific journal
• Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice
  Takeshi Nakamura; Shinichi Miyagawa; Yoshinao Katsu; Hajime Watanabe; Takeshi Mizutani; Tomomi Sato; Ken-Ichirou Morohashi; Takashi Takeuchi; Taisen Iguchi; Yasuhiko Ohta
  TOXICOLOGY, 296, 1-3, 13, 19, Jun. 2012, [Peer-reviewed]
  English, Scientific journal
• Gene expression profiles in the testis associated with testis-ova in adult Japanese medaka (Oryzias latipes) exposed to 17 alpha-ethinylestradiol
  Ikumi Hirakawa; Shinichi Miyagawa; Yoshinao Katsu; Yoshihiro Kagami; Norihisa Tatarazako; Tohru Kobayashi; Teruhiko Kusano; Takeshi Mizutani; Yukiko Ogino; Takashi Takeuchi; Yasuhiko Ohta; Taisen Iguchi
  CHEMOSPHERE, 87, 7, 668, 674, May 2012, [Peer-reviewed]
  English, Scientific journal
• Comparative responsiveness to natural and synthetic estrogens of fish species commonly used in the laboratory and field monitoring
  Anke Lange; Yoshinao Katsu; Shinichi Miyagawa; Yukiko Ogino; Hiroshi Urushitani; Tohru Kobayashi; Toshiaki Hirai; Janice A. Shears; Masaki Nagae; Jun Yamamoto; Yuta Ohnishi; Tomohiro Oka; Norihisa Tatarazako; Yasuhiko Ohta; Charles R. Tyler; Taisen Iguchi
  AQUATIC TOXICOLOGY, 109, 250, 258, Mar. 2012, [Peer-reviewed]
  English, Scientific journal
• Altered gonadal expression of TGF-beta superfamily signaling factors in environmental contaminant-exposed juvenile alligators
  Brandon C. Moore; Matthew R. Milnes; Satomi Kohno; Yoshinao Katsu; Taisen Iguchi; Teresa K. Woodruff; Louis J. Guillette
  JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 127, 1-2, 58, 63, Oct. 2011, [Peer-reviewed]
  English, Scientific journal
• Cloning and characterization of retinoid X receptor (RXR) isoforms in the rock shell, Thais clavigera
  Hiroshi Urushitani; Yoshinao Katsu; Yasuhiko Ohta; Hiroaki Shiraishi; Taisen Iguchi; Toshihiro Horiguchi
  AQUATIC TOXICOLOGY, 103, 1-2, 101, 111, May 2011, [Peer-reviewed]
  English, Scientific journal
• Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring
  Andrew D. Southam; Anke Lange; Adam Hines; Elizabeth M. Hill; Yoshinao Katsu; Taisen Iguchi; Charles R. Tyler; Mark R. Viant
  ENVIRONMENTAL SCIENCE & TECHNOLOGY, 45, 8, 3759, 3767, Apr. 2011, [Peer-reviewed]
  English, Scientific journal
• Estrogen receptors in medaka (Oryzias latipes) and estrogenic environmental contaminants: An in vitro-in vivo correlation
  Tapas Chakraborty; Yoshinao Katsu; Lin Yan Zhou; Shinichi Miyagawa; Yoshitaka Nagahama; Taisen Iguchi
  JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 123, 3-5, 115, 121, Feb. 2011, [Peer-reviewed]
  English, Scientific journal
• Differential expression of three estrogen receptor subtype mRNAs in gonads and liver from embryos to adults of the medaka, Oryzias latipes
  Tapas Chakraborty; Yasushi Shibata; Lin-Yan Zhou; Yoshinao Katsu; Taisen Iguchi; Yoshitaka Nagahama
  MOLECULAR AND CELLULAR ENDOCRINOLOGY, 333, 1, 47, 54, Feb. 2011, [Peer-reviewed]
  English, Scientific journal
• Molecular cloning of anti-Mullerian hormone from the American alligator, Alligator mississippiensis
  Hiroshi Urushitani; Yoshinao Katsu; Shinichi Miyagawa; Satomi Kohno; Yasuhiko Ohta; Louis J. Guillette; Taisen Iguchi
  MOLECULAR AND CELLULAR ENDOCRINOLOGY, 333, 2, 190, 199, Feb. 2011, [Peer-reviewed]
  English, Scientific journal
• Molecular Cloning, Characterization, and Chromosome Mapping of Reptilian Estrogen Receptors
  Yoshinao Katsu; Kazumi Matsubara; Satomi Kohno; Yoichi Matsuda; Michihisa Toriba; Kaori Oka; Louis J. Guillette; Yasuhiko Ohta; Taisen Iguchi
  ENDOCRINOLOGY, 151, 12, 5710, 5720, Dec. 2010, [Peer-reviewed]
  English, Scientific journal
• Transcriptional activity and biological effects of mammalian estrogen receptor ligands on three hepatic estrogen receptors in Mozambique tilapia
  L. K. Davis; Y. Katsu; T. Iguchi; D. T. Lerner; T. Hirano; E. G. Grau
  JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 122, 4, 272, 278, Oct. 2010, [Peer-reviewed]
  English, Scientific journal
• Molecular cloning and characterization of ligand- and species-specificity of amphibian estrogen receptors
  Yoshinao Katsu; Ena Taniguchi; Hiroshi Urushitani; Shinichi Miyagawa; Minoru Takase; Kaoru Kubokawa; Osamu Tooi; Tomohiro Oka; Noriaki Santo; Jan Myburgh; Akira Matsuno; Taisen Iguchi
  GENERAL AND COMPARATIVE ENDOCRINOLOGY, 168, 2, 220, 230, Sep. 2010, [Peer-reviewed]
  English, Scientific journal
• Cloning and functional characterization of Chondrichthyes, cloudy catshark, Scyliorhinus torazame and whale shark, Rhincodon typus estrogen receptors
  Yoshinao Katsu; Satomi Kohno; Haruka Narita; Hiroshi Urushitani; Koudai Yamane; Akihiko Hara; Tonya M. Clauss; Michael T. Walsh; Shinichi Miyagawa; Louis J. Guillette; Taisen Iguchi
  GENERAL AND COMPARATIVE ENDOCRINOLOGY, 168, 3, 496, 504, Sep. 2010, [Peer-reviewed]
  English, Scientific journal
• Estrogen Receptor ESR1 Is Indispensable for the Induction of Persistent Vaginal Change by Neonatal 5alpha-Dihydrotestosterone Exposure in Mice
  Shinichi Miyagawa; Yoshinao Katsu; Yasuhiko Ohta; Tamotsu Sudo; Dennis B. Lubahn; Taisen Iguchi
  BIOLOGY OF REPRODUCTION, 82, 3, 497, 503, Mar. 2010, [Peer-reviewed]
  English, Scientific journal
• Potential Contributions of Heat Shock Proteins to Temperature-Dependent Sex Determination in the American Alligator
  S. Kohno; Y. Katsu; H. Urushitani; Y. Ohta; T. Iguchi; L. J. Guillette
  SEXUAL DEVELOPMENT, 4, 1-2, 73, 87, Mar. 2010, [Peer-reviewed]
  English, Scientific journal
• Estrogen-Dependent Transactivation of Amphioxus Steroid Hormone Receptor via Both Estrogen and Androgen Response Elements
  Yoshinao Katsu; Kaoru Kubokawa; Hiroshi Urushitani; Taisen Iguchi
  ENDOCRINOLOGY, 151, 2, 639, 648, Feb. 2010, [Peer-reviewed]
  English, Scientific journal
• Influences of Sex, Incubation Temperature, and Environmental Quality on Gonadal Estrogen and Androgen Receptor Messenger RNA Expression in Juvenile American Alligators (Alligator mississippiensis)
  Brandon C. Moore; Matthew R. Milnes; Satomi Kohno; Yoshinao Katsu; Taisen Iguchi; Louis J. Guillette
  BIOLOGY OF REPRODUCTION, 82, 1, 194, 201, Jan. 2010, [Peer-reviewed]
  English, Scientific journal
• Environmental Health Impacts of Equine Estrogens Derived from Hormone Replacement Therapy
  Charles R. Tyler; Amy L. Filby; Lisa K. Bickley; Rob I. Cumming; Richard Gibson; Pierre Labadie; Yoshinao Katsu; Katherine E. Liney; Janice A. Shears; Vanessa Silva-Castro; Hiroshi Urushitani; Anke Lange; Matthew J. Winter; Taisen Iguchi; Elizabeth M. Hill
  ENVIRONMENTAL SCIENCE & TECHNOLOGY, 43, 10, 3897, 3904, May 2009, [Peer-reviewed]
  English, Scientific journal
• Sexual Reprogramming and Estrogenic Sensitization in Wild Fish Exposed to Ethinylestradiol
  Anke Lange; Gregory C. Paull; Tobias S. Coe; Yoshinao Katsu; Hiroshi Urushitani; Taisen Iguchi; Charles R. Tyler
  ENVIRONMENTAL SCIENCE & TECHNOLOGY, 43, 4, 1219, 1225, Feb. 2009, [Peer-reviewed]
  English, Scientific journal
• From Reptilian Phylogenomics to Reptilian Genomes: Analyses of c-Jun and DJ-1 Proto-Oncogenes
  Y. Katsu; E. L. Braun; L. J. Guillette; T. Iguchi
  CYTOGENETIC AND GENOME RESEARCH, 127, 2-4, 79, 93, 2009, [Peer-reviewed]
  English, Scientific journal
• Molecular Cloning, Characterization, and Evolutionary Analysis of Estrogen Receptors from Phylogenetically Ancient Fish
  Yoshinao Katsu; Satomi Kohno; Susumu Hyodo; Shigeho Ijiri; Shinji Adachi; Akihiko Hara; Louis J. Guillette; Taisen Iguchi
  ENDOCRINOLOGY, 149, 12, 6300, 6310, Dec. 2008, [Peer-reviewed]
  English, Scientific journal
• Commonality in Signaling of Endocrine Disruption from Snail to Human
  Taisen Iguchi; Yoshinao Katsu
  BIOSCIENCE, 58, 11, 1061, 1067, Dec. 2008, [Peer-reviewed]
  English, Scientific journal
• Altered sexual development in roach (Rutilus rutilus) exposed to environmental concentrations of the pharmaceutical 17 alpha-ethinylestradiol and associated expression dynamics of aromatases and estrogen receptors
  Anke Lange; Yoshinao Katsu; Rie Ichikawa; Gregory C. Paull; Laura L. Chidgey; Tobias S. Coe; Taisen Iguchi; Charles R. Tyler
  TOXICOLOGICAL SCIENCES, 106, 1, 113, 123, Nov. 2008, [Peer-reviewed]
  English, Scientific journal
• The influence of non-toxic concentrations of DDT and DDE on the old world vulture estrogen receptor alpha
  Vinny Naidoo; Yoshinao Katsu; Taisen Iguchi
  GENERAL AND COMPARATIVE ENDOCRINOLOGY, 159, 2-3, 188, 195, Nov. 2008, [Peer-reviewed]
  English, Scientific journal
• Estrogen receptor subtypes selectively mediate female mouse reproductive abnormalities induced by neonatal exposure to estrogenic chemicals
  Takeshi Nakamura; Yoshinao Katsu; Hajime Watanabe; Taisen Iguchi
  TOXICOLOGY, 253, 1-3, 117, 124, Nov. 2008, [Peer-reviewed]
  English, Scientific journal
• Toxicogenomics and Ecotoxicogenomics: Studying Chemical Effects and Basic Biology in Vertebrates and Invertebrates
  Taisen Iguchi; Hajime Watanabe; Yoshinao Katsu
  Toxicogenomics: A Powerful Tool for Toxicity Assessment, 143, 158, John Wiley and Sons, 14 Oct. 2008, [Peer-reviewed]
  English, In book
• Novel approaches for the study of vertebrate steroid hormone receptors
  Satomi Kohno; Yoshinao Katsu; Taisen Iguchi; Louis J. Guillette
  INTEGRATIVE AND COMPARATIVE BIOLOGY, 48, 4, 527, 534, Oct. 2008, [Peer-reviewed]
  English, Scientific journal
• Activation of steroid and xenobiotic receptor (SXR, NR1I2) and its orthologs in laboratory, toxicologic, and genome model species
  Matthew R. Milnes; Adriana Garcia; Emily Grossman; Felix Grun; Jason Shiotsugu; Michelle M. Tabb; Yukio Kawashima; Yoshinao Katsu; Hajime Watanabe; Taisen Iguchi; Bruce Blumberg
  ENVIRONMENTAL HEALTH PERSPECTIVES, 116, 7, 880, 885, Jul. 2008, [Peer-reviewed]
  English, Scientific journal
• Gene expression patterns in juvenile American alligators (Alligator mississippiensis) exposed to environmental contaminants
  Satomi Kohno; Dieldrich S. Bermudez; Yoshinao Katsu; Taisen Iguchi; Louis J. Guillette
  AQUATIC TOXICOLOGY, 88, 2, 95, 101, Jun. 2008, [Peer-reviewed]
  English, Scientific journal
• Increased posthatching mortality and loss of sexually dimorphic gene expression in alligators (Alligator mississippiensis) from a contaminated environment
  Matthew R. Milnes; Teresa A. Bryan; Yoshinao Katsu; Satomi Kohno; Brandon C. Moore; Taisen Iguchi; Louis J. Guillette
  BIOLOGY OF REPRODUCTION, 78, 5, 932, 938, May 2008, [Peer-reviewed]
  English, Scientific journal
• Molecular cloning and characterization of estrogen, androgen, and progesterone nuclear receptors from a freshwater turtle (Pseudemys nelsoni)
  Yoshinao Katsu; Rie Ichikawa; Toshitaka Ikeuchi; Satomi Kohno; Louis J. Guillette; Taisen Iguchi
  ENDOCRINOLOGY, 149, 1, 161, 173, Jan. 2008, [Peer-reviewed]
  English, Scientific journal
• Vacuolar degeneration of skeletal muscle in transgenic mice overexpressing ORP150
  Tomohiro Kobayashi; Yuko Takita; Atsuko Suzuki; Yoshinao Katsu; Taisen Iguchi; Yasuhiko Ohta
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 70, 1, 115, 118, Jan. 2008, [Peer-reviewed]
  English, Scientific journal
• In vitro assessment of transcriptional activation of the estrogen and androgen receptors of mosquitofish, Gambusia affinis affinis
  Yoshinao Katsu; Megumi Hinago; Kiyoaki Sone; Hiroshi Urushitani; Louis J. Guillette; Taisen Iguchi
  MOLECULAR AND CELLULAR ENDOCRINOLOGY, 276, 1-2, 10, 17, Sep. 2007, [Peer-reviewed]
  English, Scientific journal
• Patterns of vertebrate isochore evolution revealed by comparison of expressed mammalian, avian, and crocodilian genes
  Jena L. Chojnowski; James Franklin; Yoshinao Katsu; Taisen Iguchi; Louis J. Guillette; Rebecca T. Kimball; Edward L. Braun
  JOURNAL OF MOLECULAR EVOLUTION, 65, 3, 259, 266, Sep. 2007, [Peer-reviewed]
  English, Scientific journal
• Toxicogenomics and ecotoxicogenomics for studying endocrine disruption and basic biology
  Taisen Iguchi; Hajime Watanabe; Yoshinao Katsu
  GENERAL AND COMPARATIVE ENDOCRINOLOGY, 153, 1-3, 25, 29, Aug. 2007, [Peer-reviewed]
  English, Scientific journal
• Functional associations between two estrogen receptors, environmental estrogens, and sexual disruption in the roach (Rutilus rutilus)
  Yoshinao Katsu; Anke Lange; Hiroshi Urushitani; Rie Ichikawa; Gregory C. Paull; Laura L. Cahill; Susan Jobling; Charles R. Tyler; Taisen Iguchi
  ENVIRONMENTAL SCIENCE & TECHNOLOGY, 41, 9, 3368, 3374, May 2007, [Peer-reviewed]
  English, Scientific journal
• Medaka (Oryzias latipes) for use in evaluating developmental effects of endocrine active chemicals with special reference to gonadal intersex (testis-ova).
  Urushitani H; Katsu Y; Kato Y; Tooi O; Santo N; Kawashima Y; Ohta Y; Kisaka Y; Lange A; Tyler CR; Johnson RD; Iguchi T
  Environmental sciences : an international journal of environmental physiology and toxicology, 14, 211, 233, 5, 2007, [Peer-reviewed]
• The roach (Rutilus rutilus) as a sentinel for assessing endocrine disruption.
  Tyler CR; Lange A; Paull GC; Katsu Y; Iguchi T
  Environmental sciences : an international journal of environmental physiology and toxicology, 14, 235, 253, 5, 2007, [Peer-reviewed]
• Cloning and differential expression of estrogen receptor and aromatase genes in the self-fertilizing hermaphrodite and male mangrove rivulus, Kryptolebias marmoratus
  Edward F. Orlando; Yoshinao Katsu; Shinichi Miyagawa; Taisen Iguchi
  JOURNAL OF MOLECULAR ENDOCRINOLOGY, 37, 2, 353, 365, Oct. 2006, [Peer-reviewed]
  English, Scientific journal
• Molecular cloning of estrogen receptor alpha (ER alpha; ESR1) of the Japanese giant salamander, Andrias japonicus
  Yoshinao Katsu; Satomi Kohno; Tomohiro Oka; Naoko Mitsui; Osamu Tooi; Noriaki Santo; Hiroshi Urushitani; Yukio Fukumoto; Kazushi Kuwabara; Kazuhide Ashikaga; Shinji Minami; Shigeaki Kato; Yasuhiko Ohta; Louis J. Guillette; Taisen Iguchi
  MOLECULAR AND CELLULAR ENDOCRINOLOGY, 257-8, 84, 94, Sep. 2006, [Peer-reviewed]
  English, Scientific journal
• Effects of bisphenol A given neonatally on reproductive functions of male rats
  Hideo Kato; Tadakazu Furuhashi; Masami Tanaka; Yoshinao Katsu; Hajime Watanabe; Yasuhiko Ohta; Taisen Iguchi
  REPRODUCTIVE TOXICOLOGY, 22, 1, 20, 29, Jul. 2006, [Peer-reviewed]
  English, Scientific journal
• Phosphorylation of the p34(cdc2) target site on goldfish germinal vesicle lamin B3 before oocyte maturation
  A Yamaguchi; Y Katsu; M Matsuyama; M Yoshikuni; Y Nagahama
  EUROPEAN JOURNAL OF CELL BIOLOGY, 85, 6, 501, 517, Jun. 2006, [Peer-reviewed]
  English, Scientific journal
• Tissue-specific expression of Clec2g in mice
  Y Katsu; T Iguchi
  EUROPEAN JOURNAL OF CELL BIOLOGY, 85, 5, 345, 354, May 2006, [Peer-reviewed]
  English, Scientific journal
• Application of ecotoxicogenomics for studying endocrine disruption in vertebrates and invertebrates
  Taisen Iguchi; Hajime Watanabe; Yoshinao Katsu
  ENVIRONMENTAL HEALTH PERSPECTIVES, 114, 101, 105, Apr. 2006, [Peer-reviewed]
  English, Scientific journal
• Molecular cloning of estrogen receptor alpha of the Nile crocodile
  Y Katsu; J Myburgh; S Kohno; GE Swan; LJ Guillette; T Iguchi
  COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, 143, 3, 340, 346, Mar. 2006, [Peer-reviewed]
  English, Scientific journal
• Ontogenic expression of estrogen receptor-alpha in female rat corneas
  Hideo Kato; Kazuyoshi Naito; Yoshinao Katsu; Hajime Watanabe; Yasuhiko Ohta; Taisen Iguchi
  OPHTHALMIC RESEARCH, 38, 6, 361, 365, 2006, [Peer-reviewed]
  English, Scientific journal
• Effects of an androgenic growth promoter 17 beta-trenbolone on masculinization of mosquitofish (Gambusia affinis affinis)
  K Sone; M Hinago; M Itamoto; Y Katsu; H Watanabe; H Urushitani; O Tooi; LJ Guillette; T Iguchi
  GENERAL AND COMPARATIVE ENDOCRINOLOGY, 143, 2, 151, 160, Sep. 2005, [Peer-reviewed]
  English, Scientific journal
• Phosphorylation of the p34(cdc2) target site on goldfish germinal vesicle lamin B3 before oocyte maturation
  Akihiko Yamaguchi; Yoshinao Katsu; Michiyasu Yoshikuni; Michiya Matsuyama; Yoshitaka Nagahama
  CELL STRUCTURE AND FUNCTION, 29, 65, 65, May 2004, [Peer-reviewed]
  English
• Persistent gene expression in mouse vagina exposed neonatally to diethylstilbestrol
  S. Miyagawa; A. Suzuki; Y. Katsu; M. Kobayashi; M. Goto; H. Handa; H. Watanabe; T. Iguchi
  J Mol Endocrinol, 32, 663, 677, Apr. 2004, [Peer-reviewed]
  English, Scientific journal
• Evaluation of estrogenic activity in diets for experimental animals using in vitro assay
  H Kato; T Iwata; Y Katsu; H Watanabe; Y Ohta; T Iguchi
  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 52, 5, 1410, 1414, Mar. 2004, [Peer-reviewed]
  English, Scientific journal
• Estrogen-independent activation of erbBs signaling and estrogen receptor alpha in the mouse vagina exposed neonatally to diethylstilbestrol
  S Miyagawa; Y Katsu; H Watanabe; T Iguchi
  ONCOGENE, 23, 2, 340, 349, Jan. 2004, [Peer-reviewed]
  English, Scientific journal
• Bisphenol A exerts thyroid-hormone-like effects on mouse oligodendrocyte precursor cells
  C Seiwa; J Nakahara; T Komiyama; Y Katsu; T Iguchi; H Asou
  NEUROENDOCRINOLOGY, 80, 1, 21, 30, 2004, [Peer-reviewed]
  English, Scientific journal
• Involvement of Xenopus Pumilio in the translational regulation that is specific to cyclin B1 mRNA during oocyte maturation
  S Nakahata; T Kotani; K Mita; T Kawasaki; Y Katsu; Y Nagahama; M Yamashita
  MECHANISMS OF DEVELOPMENT, 120, 8, 865, 880, Aug. 2003, [Peer-reviewed]
  English, Scientific journal
• Expression of a novel C-type lectin in the mouse vagina
  Y Katsu; DB Lubahn; T Iguchi
  ENDOCRINOLOGY, 144, 6, 2597, 2605, Jun. 2003, [Peer-reviewed]
  English, Scientific journal
• Cloning and characterization of estrogen receptor alpha in mummichog, Fundulus heteroclitus
  H Urushitani; M Nakai; H Inanaga; Y Shimohigashi; A Shimizu; Y Katsu; T Iguchi
  MOLECULAR AND CELLULAR ENDOCRINOLOGY, 203, 1-2, 41, 50, May 2003, [Peer-reviewed]
  English, Scientific journal
• Early estrogen exposure induces abnormal development of Fundulus heteroclitus
  H Urushitani; A Shimizu; Y Katsu; T Iguchi
  JOURNAL OF EXPERIMENTAL ZOOLOGY, 293, 7, 693, 702, Dec. 2002, [Peer-reviewed]
  English, Scientific journal
• Estrogen-independent expression of neuropsin, a serine protease in the vagina of mice exposed neonatally to diethylstilbestrol
  Y Katsu; E Takasu; T Iguchi
  MOLECULAR AND CELLULAR ENDOCRINOLOGY, 195, 1-2, 99, 107, Sep. 2002, [Peer-reviewed]
  English, Scientific journal
• Bisphenol-A administration during pregnancy results in fetal exposure in mice and monkeys
  K. Uchida; A. Suzuki; Y. Kobayashi; D. L. Buchanan; T. Sato; H. Watanabe; Y. Katsu; J. Suzuki; K. Asaoka; C. Mori; K. Arizono; T. Iguchi
  Journal of Health Science, 48, 6, 579, 582, The Pharmaceutical Society of Japan, Apr. 2002, [Peer-reviewed]
  English, Scientific journal, Placental transfer of bisphenol-A (BPA) was studied in mice and Japanese monkeys (Macaca fuscata). BPA was found in maternal and fetal sera, liver, brain, uteri, testes and placenta as early as 30 min after a single subcutaneous (s.c.) injection to 17 days of pregnancy in mice. BPA was also found in fetal liver, kidney, and brain of Japanese monkeys 1 hr after a single s.c. injection to 150 days of pregnancy. These results clearly indicate that the maternal placental barrier can not protect the fetus from the consequences of BPA exposure in these species.
  
• Developmental effects of perinatal exposure to bisphenol-A and diethylstilbestrol on reproductive organs in female mice
  A Suzuki; A Sugihara; K Uchida; T Sato; Y Ohta; Y Katsu; H Watanabe; T Iguchi
  REPRODUCTIVE TOXICOLOGY, 16, 2, 107, 116, Mar. 2002, [Peer-reviewed]
  English, Scientific journal
• Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on female mouse reproduction
  S Honma; A Suzuki; DL Buchanan; Y Katsu; H Watanabe; T Iguchi
  REPRODUCTIVE TOXICOLOGY, 16, 2, 117, 122, Mar. 2002, [Peer-reviewed]
  English, Scientific journal
• Developmental toxicity of estrogenic chemicals on rodents and other species
  Taisen Iguchi; Hajime Watanabe; Yoshinao Katsu; Takeshi Mizutani; Shinichi Miyagawa; Atsuko Suzuki; Satomi Kohno; Kiyoaki Sone; Hideo Kato
  Congenital anomalies, 42, 2, 94, 105, 2, 2002, [Peer-reviewed]
  English
• Immunological detection and characterization of poly(A) polymerase, poly(A)-binding protein and cytoplasmic polyadenylation element-binding protein in goldfish and Xenopus oocytes
  Nakahata S; Mita K; Katsu Y; Nagahama Y; Yamashita M
  Zoological Science, 18, 3, 337, 343, Zoological Society of Japan, 2001, [Peer-reviewed]
  English, Cytoplasmic polyadenylation regulates translational activation of dormant cyclin B1 mRNA stored in immature oocytes, a process required for the initiation of oocyte maturation in goldfish and Xenopus. As a first step towards understanding the molecular mechanisms of translational activation of cyclin B1 during oocyte maturation, we have isolated cDNA clones encoding proteins involved in cytoplasmic polyadenylation and produced specific antibodies against recombinant proteins. These include poly (A) polymerase (PAP), poly(A)-binding protein (PABP) and cytoplasmic polyadenylation element-binding protein (CPEB). Monoclonal antibodies raised against goldfish PAP recognized several forms of PAP in goldfish and Xenopus oocytes. Besides ordinary PAPs with high molecular weight (ca. 100 kDa), the antibodies also detected those with low molecular weight (ca. 40 kDa) that are present specifically in the cytoplasm, raising new players that might be responsible for cytoplasmic polyadenylation. An antibody against goldfish PABP showed for the first time in Xenopus oocytes the protein expression of PABPII, another PABP distinct from the well-characterized PABPI. Monoclonal antibodies raised against Xenopus CPEB recognized both unphosphorylated 62-kDa and phosphorylated 64-kDa forms but did not cross-react with goldfish CPEB, which was specifically detected by anti-goldfish CPEB monoclonal antibodies produced previously. The cDNAs, recombinant proteins and antibodies produced in this study are expected to provide useful tools for investigating the regulatory mechanisms of cyclin B1 translation during oocyte maturation in goldfish and Xenopus.
• Biochemical identification of Xenopus pumilio as a sequence-specific cyclin B1 mRNA-binding protein that physically interacts with a nanos homolog, Xcat-2, and a cytoplasmic polyadenylation element-binding protein
  Nakahata S; Katsu Y; Mita K; Inoue K; Nagahama Y; Yamashita M
  Journal of Biological Chemistry, 276, 24, 20945, 20953, 2001, [Peer-reviewed]
• Ca2+ is required for phosphorylation of clam p82/CPEB in vitro: Implications for dual and independent roles of MAP and Cdc2 kinases
  Y Katsu; N Minshall; Y Nagahama; N Standart
  DEVELOPMENTAL BIOLOGY, 209, 1, 186, 199, May 1999, [Peer-reviewed]
  English, Scientific journal
• Translational regulation of cyclin B mRNA by 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (maturation-inducing hormone) during oocyte maturation in a teleost fish, the goldfish (Carassius auratus)
  Katsu Y; Yamashita M; Nagahama Y
  Molecular and Cellular Endocrinology, 158, 1-2, 79, 85, 1999, [Peer-reviewed]
• Isolation and characterization of goldfish Y box protein, a germ-cell-specific RNA-binding protein
  Katsu Y; Yamashita M; Nagahama Y
  European Journal of Biochemistry, 249, 3, 854, 861, 1997, [Peer-reviewed]
• Initiation of cyclin B degradation by the 26S proteasome upon egg activation
  Tokumoto T; Yamashita M; Tokumoto M; Katsu Y; Horiguchi R; Kajiura H; Nagahama Y
  Journal of Cell Biology, 138, 6, 1313, 1322, 1997, [Peer-reviewed]
• REGULATION OF OOCYTE GROWTH AND MATURATION IN FISH
  NAGAHAMA Y; YOSHIKUNI M; YAMASHITA M; TOKUMOTO T; KATSU Y
  Current Topics in Develop. Biol., 30, 103, 145, 1995, [Peer-reviewed]
• MOLECULAR-CLONING AND IMMUNOLOGICAL ANALYSIS OF GOLDFISH CYCLIN-A DURING OOCYTE MATURATION
  KATSU Y; YAMASHITA M; HIRAI T; TOKUMOTO T; KAJIURA H; NAGAHAMA Y
  Developmental Biology, 170, 2, 616, 625, 1995, [Peer-reviewed]
• ISOLATION AND CHARACTERIZATION OF GOLDFISH CDC2, A CATALYTIC COMPONENT OF MATURATION-PROMOTING FACTOR
  KAJIURA H; YAMASHITA M; KATSU Y; NAGAHAMA Y
  Development Growth & Differentiation, 35, 6, 647, 654, 1993, [Peer-reviewed]
• BEHAVIOR OF THE COMPONENTS OF MATURATION-PROMOTING FACTOR, CDC2 KINASE AND CYCLIN-B, DURING OOCYTE MATURATION OF GOLDFISH
  KATSU Y; YAMASHITA M; KAJIURA H; NAGAHAMA Y
  Developmental Biology, 160, 1, 99, 107, 1993, [Peer-reviewed]
• A FISH HOMOLOG OF THE CDC2-RELATED PROTEIN P40(MO15) - ITS CDNA CLONING AND EXPRESSION IN OOCYTES
  ONOE S; YAMASHITA M; KAJIURA H; KATSU Y; JIANG JQ; NAGAHAMA Y
  Biomedical Research-Tokyo, 14, 6, 441, 444, 1993, [Peer-reviewed]
• MEIOSIS-REINITIATION-INDUCING FACTOR OF TETRAHYMENA FUNCTIONS UPSTREAM OF M-PHASE-PROMOTING FACTOR
  M FUJISHIMA; Y KATSU; E OGAWA; M SAKIMURA; M YAMASHITA; Y NAGAHAMA
  JOURNAL OF PROTOZOOLOGY, 39, 6, 683, 690, Nov. 1992, [Peer-reviewed]
  English, Scientific journal
• INDUCTION OF REINITIATION OF MEIOSIS IN AMPHIBIAN BUFO AND XENOPUS OOCYTES BY INJECTION OF M-PHASE EXTRACTS OF CILIATE TETRAHYMENA NEEDS THE RECIPIENT PROTEIN-SYNTHESIS
  M FUJISHIMA; KODAMA, I; M HORI; M HORI; Y KATSU; R IMAI
  EXPERIMENTAL CELL RESEARCH, 193, 1, 155, 160, Mar. 1991, [Peer-reviewed]
  English, Scientific journal

• 軟体動物前鯉類RXRの転写活性誘導における有機スズ化合物の影響
  漆谷博志; 勝義直; 太田康彦; 白石寛明; 井口泰泉; 堀口敏宏, 環境ホルモン学会研究発表会プログラム・要旨集, 16th, 2013
• 軟体動物前鰓類RXRを用いた有機スズ化合物による転写活性誘導差異
  漆谷博志; 勝義直; 勝義直; 太田康彦; 白石寛明; 井口泰泉; 堀口敏宏, 環境ホルモン学会研究発表会プログラム・要旨集, 15th, 2012
• レポータージーンアッセイ法を用いたイボニシ貝新規RAR様遺伝子の性状決定
  漆谷博志; 勝義直; 太田康彦; 白石寛明; 井口泰泉; 堀口敏宏, 環境ホルモン学会研究発表会プログラム・要旨集, 14th, 2011
• イボニシ貝新規RXR遺伝子を用いたレポータージーンアッセイ法等による性状決定
  漆谷博志; 勝義直; 太田康彦; 井口泰泉; 白石寛明; 堀口敏宏, 環境ホルモン学会研究発表会プログラム・要旨集, 13th, 2010
• 両生類女性ホルモン受容体の種特異性及びリガンド特異性
  宮川信一; 勝義直; 井口泰泉, 比較内分泌学, 36, 139, 283, 285, 2010
  日本比較内分泌学会, Japanese
• レポータージーンアッセイを利用した魚類エストロゲン受容体の種特異性.
  勝義直; 井口泰泉, 環境ホルモン学会ニュースレター, 10, 4, 6, 2008
• Commonality and difference in mechanisms of endocrine disruption in various animal species.
  Iguchi, T; Katsu, Y, BioScience, 58, 1061, 1067, 2008
• Developmental reproductive effects of exposure to pharmaceutical steroids in the aquatic environment: Studies on mosquitofish (Gambusia affinis affinis), roach (Rutilus rutilus) and medaka (Oryzias latipes).
  Iguchi, T; Katsu, Y; Urushitani, H; Lange, A; Tyler, C.R, J. Marine Sci. Technol., 15, 29, 36, 2007
• Analysis of the ligand-specificity of the estrogen and androgen receptors of mosquitofish, Gambusia affinis affinis.
  Katsu, Y; Hinago, M; Sone, K; Guillette, L.J.Jr; Iguchi, T, Mol. Cell. Endocrinol., 276, 10, 17, 2007
• Endocrine disrupting organotin compounds are potent inducers of imposex in gastropods and adipogenesis in vertebrates.
  Iguchi, T; Katsu, Y; Horiguchi, T; Watanabe, H; Blumberg, B; Ohta, Y, Mol. Cell. Toxicol., 3, 1, 10, 2007
• Molecular cloning of estrogen receptor A and B of raucous toad
  Ena Taniguchi; Yoshinao Katsu; Noriaki Santou; Osamu Tooi; Taisen Iguchi; Akira Matsuno, ZOOLOGICAL SCIENCE, 23, 12, 1213, 1213, Dec. 2006
  English, Summary international conference
• Molecular cloning and expression of DM domain genes from the water flea, Daphnia magna
  Yasuhiko Kato; Kaoru Kobayashi; Yoshinao Katsu; Hajime Watanabe; Taisen Iguchi, ZOOLOGICAL SCIENCE, 23, 12, 1182, 1182, Dec. 2006
  English, Summary international conference
• Moelcular cloning of reptile steroid hormone receptors
  Yoshinao Katsu; Rie Ichikawa; Toshitaka Ikeuchi; Louis Guillette; Taisen Iguchi, ZOOLOGICAL SCIENCE, 23, 12, 1216, 1216, Dec. 2006
  English, Summary international conference
• Expression of wnt family genes in mouse vagina exposed neonatally to diethylstilbestrol
  Takeshi Nakamura; Yoshinao Katsu; Hajime Watanabe; Taisen Iguchi, ZOOLOGICAL SCIENCE, 23, 12, 1216, 1216, Dec. 2006
  English, Summary international conference
• Molecular cloning of the estrogen and progesterone receptors of the American alligator
  Y Katsu; DS Bermudez; EL Braun; C Helbing; S Miyagawa; MP Gunderson; S Kohno; TA Bryan; LJ Guillette; T Iguchi, GENERAL AND COMPARATIVE ENDOCRINOLOGY, 136, 1, 122, 133, Mar. 2004
  English
• Estrogen Receptor Binding Assay for Evaluation of Endocrine Disrupting Chemicals on Marine Fish
  Nakai M; Yokota H; Urushitani H; Asai D; Katsu Y; Eto C; Yakabe Y; Iguchi T; Shimohigashi Y, Marine Biotechnology, 6, S137-141, 2004
• Estrogenic Regulation of Gene Expression of Ras Family (ENDOCRINE SYSTEM) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
  Kato Hideo; Ohta Yasuhiko; Katsu Yoshinao; Watanabe Hajime; Iguchi Taisen, Journal of toxicological sciences, 28, 4, 319, 319, 31 Oct. 2003
  The Japanese Society of Toxicology, English
• CLONING, EXPRESSION, AND CHARACTERIZATION OF ESTROGEN RECEPTOR ALPHA mRNA IN MUMMICHOG, FUNDULUS HETEROCLITUS
  URUSHITANI H.; NAKAI M.; INANAGA H.; SHIMOHIGASHI Y.; SHIMIZU A.; KATSU Y.; IGUCHI T., Proceedings of the Japan Society for Comparative Endocrinology, 18, 63, 63, 08 Aug. 2003
  English
• MOLECULAR CLONING OF THE ESTROGEN RECEPTOR, C-JUN AND DJ-1 OF THE AMERICAN ALLIGATOR
  KATSU Yoshinao; GUNDERSON Mark; GUILLETTE JR. Louis J.; IGUCHI Taisen, Proceedings of the Japan Society for Comparative Endocrinology, 18, 69, 69, 08 Aug. 2003
  English
• A NOVEL C-TYPE LECTIN EXPRESSION IN STRATIFIED AND CORNIFIED EPITHELIAL CELLS(Endocrinology,Abstracts of papers presented at the 74^ Annual Meeting of the Zoological Society of Japan) :
  Katsu Yoshinao; Iguchi Taisen, Zoological science, 20, 12, 1611, 1611, 2003
  Zoological Society of Japan, English
• ESTROGEN-INDEPENDENT ACTIVATION OF ErbBs SIGNALING AND ESTROGEN RECEPTOR α IN THE MOUSE VAGINA EXPOSED NEONATALLY TO DIETHYLSTILBESTROL(Endocrinology,Abstracts of papers presented at the 74^ Annual Meeting of the Zoological Society of Japan) :
  Miyagawa Shinichi; Katsu Yoshinao; Watanabe Hajime; Iguchi Taisen, Zoological science, 20, 12, 1606, 1606, 2003
  Zoological Society of Japan, English
• A NOVEL C-TYPE LECTIN IDENTIFIED IN THE MOUSE VAGINA(Endocrinology)(Proceedings of the Seventy-Third Annual Meeting of the Zoological Society of Japan) :
  Katsu Yoshinao; Iguchi Taisen, Zoological science, 19, 12, 1491, 1491, 2002
  Zoological Society of Japan, English
• CHANGES IN EXPRESSION OF ErbBs AND THEIR LIGANDS IN NEONATALLY DES-EXPOSED MOUSE VAGINA(Endocrinology)(Proceedings of the Seventy-Third Annual Meeting of the Zoological Society of Japan) :
  Miyagawa Shinichi; Katsu Yoshinao; Watanabe Hajime; Iguchi Taisen, Zoological science, 19, 12, 1492, 1492, 2002
  Zoological Society of Japan, English
• Developmental effects of estrogenic agents on mouse reproductive tracts(IV. Reproductive embryotoxicology : Present and future)
  Iguchi T.; Katsu Y.; Watanabe H., Congenital anomalies, 41, 3, 233, 234, Sep. 2001
  The Japanese Teratology Society, English
• A novel C-type lectin identified in the mouse vagina by differential display.(Endocrinology)(Proceeding of the Seventy-Third Annual Meeting of the Zoological Society of Japan) :
  Katsu Y.; Takasu E.; Watanabe H.; Iguchi T., Zoological science, 18, 13, 13, 2001
  Zoological Society of Japan, English
• XENOPUS PUMILIO HAS A ROLE IN TRANSLATIONAL REPRESSION OF CYCLIN B1 mRNA(Developmental Biology)(Proceeding of the Seventy-Third Annual Meeting of the Zoological Society of Japan) :
  Nakahata Shingo; Mita Koichi; Katsu Yoshinao; Nagahama Yoshitaka; Yamashita Masakane, Zoological science, 18, 62, 62, 2001
  Zoological Society of Japan, English
• Characterization of protein expression in female reproductive tracts of mice exposed neonatally to diethylstilbestrol.(Endocrinology)(Proceeding of the Seventy-Third Annual Meeting of the Zoological Society of Japan) :
  Miyagawa S.; Satoh M.; Watanabe H.; Katsu Y.; Dobashi K.; Oh-Ishi M.; Maeda T.; Iguchi T., Zoological science, 18, 20, 20, 2001
  Zoological Society of Japan, English
• Developmental effects of estrogenic agents on mice, fish and frogs: a mini review.
  Iguchi, T; Watanabe, H; Katsu, Y, Horm. Behav., 40, 2, 248, 251, 2001
  Elsevier BV
• MPFとEg2によるCPEBのリン酸化
  勝義直; 山下正兼; 長浜嘉孝, 日本動物学会大会予稿集, 71st, 2000
• アフリカツメガエルPumilio蛋白質の認識配列の決定とCPEBとの相互作用
  中畑新吾; 勝義直; 長浜嘉孝; 山下正兼, 日本動物学会大会予稿集, 71st, 2000
• キンギョ卵母細胞型核ラミンB3の部位特異的リン酸化とその役割
  山口明彦; 勝義直; 長浜嘉孝, 日本動物学会大会予稿集, 71st, 2000
• XENOPUS PUMILIO IS A SEQUENCE-SPECIFIC CYCLIN B1 MRNA-BINDING PROTEIN AND INTERACTS WITH CPEB(Developmental Biology)Proceedings of the Seventy-First Annual Meeting of the Zoological Society of Japan :
  Nakahata S.; Katsu Y.; Nagahama Y.; Yamashita M., Zoological science, 17, 61, 61, 2000
  Zoological Society of Japan, English
• GOLDFISH GV LAMIN B3 : SITE-SPECIFIC PHOSPHORYLATION AND ITS POSSIBLE ROLE DURING OOCYTE MATURATION(Developmental Biology)Proceedings of the Seventy-First Annual Meeting of the Zoological Society of Japan :
  Yamaguchi Akihiko; Katsu Yoshinao; Nagahama Yoshitaka, Zoological science, 17, 57, 57, 2000
  Zoological Society of Japan, English
• PHOSPHORYLATION OF GOLDFISH CYTOPLASMIC POLYADENYLATION ELEMENT-BINDING PROTEIN(CPEB) BY EG2 AND MPF(Developmental Biology)Proceedings of the Seventy-First Annual Meeting of the Zoological Society of Japan :
  Katsu Y.; Yamashita M.; Nagahama Y., Zoological science, 17, 61, 61, 2000
  Zoological Society of Japan, English
• キンギョCPEBのクローニングとサイクリンBmRNAに存在するCPEB結合配列の解析
  勝義直; 山下正兼; 小川和男; 長浜嘉孝, 日本動物学会大会予稿集, 70th, 1999
• アフリカツメガエル卵成熟誘起におけるPumilio蛋白質の関与
  中畑新吾; 勝義直; 長浜嘉孝; 山下正兼, 日本動物学会大会予稿集, 70th, 1999
• PUMILIO IS A CANDIDATE PROTEIN INVOLVED IN TRANSLATIONAL CONTROL OF CYCLIN B1 mRNA DURING XENOPUS OOCYTE MATURATION(Developmental Biology)(Proceedings of the Seventieth Annual Meeting of the Zoological Society of Japan) :
  Nakahata S.; Katsu Y.; Nagahama Y.; Yamashita M., Zoological science, 16, 62, 62, 1999
  Zoological Society of Japan, English
• MOLECULAR CLONING OF GOLDFISH CYTOPLASMIC POLYADENYLATION ELEMENT-BINDING PROTEIN (CPEB)(Developmental Biology)(Proceedings of the Seventieth Annual Meeting of the Zoological Society of Japan) :
  Katsu Y.; Yamashita M.; Ogawa K.; Nagahama Y., Zoological science, 16, 62, 62, 1999
  Zoological Society of Japan, English
• Phosphorylation of p82 CPEB by MAP kinase and cdc2 kinase in Spisula egg.
  勝義直; CORNALL N; 長浜嘉孝; STANDART N, 日本動物学会大会予稿集, 69th, 1998
• HYPERPHOSPHORYLATION OF P82 CPEB BY MAP KINASE AND CDC2 KINASE IN THE CLAM, SPISULA SOLIDISSIMA(Developmental Biology)(Proceedings of the Sixty-Ninth Annual Meeting of the Zoological Society of Japan) :
  Katsu Y.; Cornall N.; Nagahama Y.; Standart N., Zoological science, 15, 82, 82, 1998
  Zoological Society of Japan, English
• BmRNA combined protein of cyclin.
  勝義直; 山下正兼; 長浜嘉孝, 日本動物学会大会予稿集, 67th, 1996
• Translation initiating mechanism of goldfish cyclin B in the oocyte maturation process.
  勝義直; 山下正兼; 長浜嘉孝, 日本動物学会大会予稿集, 65th, 1994
• キンギョcdc2活性化リン酸化酵素(p40^MO15)の単離
  尾上伸二; 山下正兼; 梶浦弘子; 勝義直; 長浜嘉孝, 日本動物学会大会予稿集, 64th, 1993
• キンギョサイクリンAのクローニングと卵成熟過程における変化
  勝義直; 山下正兼; 平井俊朗; 梶浦弘子; 長浜嘉孝, 日本動物学会大会予稿集, 64th, 1993
• キンギョcdc2キナーゼのcDNAクローニングと卵成熟過程における挙動
  梶浦弘子; 山下正兼; 勝義直; 長浜嘉孝, 日本動物学会大会予稿集, 64th, 1993
• キンギョcdc2活性化リン酸化酵素(p40^M015)cDNAの単離
  尾上伸二; 山下正兼; 梶浦弘子; 勝義直; 長浜嘉孝, 日本分子生物学会年会プログラム・講演要旨集, 16th, 1993
• Behavior of the components of maturation-promoting factor, cdc2 kinase and cyclin B, during oocyte maturation of goldfish
  KATSU Y., Dev Biol, 159, 1, 9, 1993
• CYCLIN B IN FISH OOCYTES : ITS APPEARANCE DURING OOCYTE MATURATION AND IMPLICATIONS FOR THE MECHANISM OF MPF ACTIVATION.(Developmental Biology)Proceedings of the Sixty-Third Annual Meeting of the Zoologiacal Socistry of Japan :
  Katsu Y.; Yamashita M.; Kajiura H.; Nagahama Y., Zoological science, 9, 6, 1162, 1162, 1992
  Zoological Society of Japan, English
• MEIOSIS-REINITIATION-INDUCING SUBSTANCE OF STARFISH OOCYTES FOUND IN PARAMECIUM : Cytology and Morphology :
  katsu Y.; Fujishima M., Zoological science, 7, 6, 1163, 1163, 1990
  Zoological Society of Japan, English

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• 生命科学特別研究, 2024年, 博士後期課程, 生命科学院
• 生物学Ⅱ, 2024年, 学士課程, 全学教育
• 生命科学文献講読, 2024年, 博士後期課程, 生命科学院
• 生殖発生生物学Ⅰ, 2024年, 学士課程, 理学部
• 機能生物学Ⅱ, 2024年, 学士課程, 理学部
• 細胞生物学Ⅱ, 2024年, 学士課程, 理学部
• 人間と文化, 2024年, 学士課程, 全学教育
• 細胞生物学Ⅲ, 2024年, 学士課程, 理学部
• 基礎形態学実習, 2024年, 学士課程, 理学部
• 基礎形態学実習, 2024年, 学士課程, 理学部

• 日本生殖内分泌学会
• JAPAN SOCIETY FOR COMPARATIVE ENDOCRINOLOGY
• 日本動物学会

• Analysis of adrenal steroid receptors in lobe-finned fish
  Grants-in-Aid for Scientific Research
  01 Apr. 2023 - 31 Mar. 2026
  勝 義直
  本研究は、「肉鰭類の副腎ステロイド受容体の解析」を目的として実施されています。ステロイドホルモン受容体は、核内受容体遺伝子スーパーファミリーに属しているホルモン依存的な転写制御因子です。そして、２つのグループである「性ステロイドホルモン受容体」と「副腎ステロイドホルモン受容体」に大別することができます。このうち「副腎ステロイドホルモン受容体」は、ヒトでは代謝・電解質制御・免疫など広範囲の生理作用に関与していることが分かっています。それでは、ヒトが持つステロイドホルモン受容体は生物進化においてどの生物の段階から出現したのでしょうか。また、ヒトで認められる受容体の生理的機能はどの生物でも同じなのでしょうか。このようなステロイドホルモン受容体それ自身と受容体が有する生理機能の成立に関わる根本的な問いかけの答えは今もって得られていません。以上のことを踏まえて、脊椎動物の進化の指標となる生物からのステロイドホルモン受容体遺伝子の単離と受容体タンパク質の機能解析を行います。特に肉鰭類であるハイギョやシーラカンスに着目しステロイドホルモン受容体の解析を進めます。
  
  
  一般的に副腎ステロイドホルモン受容体は糖質コルチコイド受容体と鉱質コルチコイド受容体の２種類が知られています。本年度は、脊椎動物の進化の指標動物である肉鰭類のハイギョから私たちのグループが単離に成功した副腎ステロイドホルモン受容体である糖質コルチコイド受容体をもちいて、様々なステロイドに対する応答を調べました。その結果、ハイギョの糖質コルチコイド受容体は、別のタイプの副腎ステロイド受容体である鉱質コルチコイド受容体のリガンド（アルドステロン）に強く応答することが判明しました。この結果は、副腎ステロイド受容体の分子進化と適応に関するこれまで知られていない重要な知見を提供するものです。
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 23K05839
• Study of functional evolution of steroid hormone receptor protein
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
  01 Apr. 2019 - 31 Mar. 2022
  Katsu Yoshinao
  In this study, we succeeded in isolating glucocorticoid, mineralocorticoid, and progesterone receptor genes from the cartilaginous fish elephant shark. This result suggests that the adrenal steroid receptor and progesterone receptor possessed in higher vertebrates such as humans are already expressed from the evolutionary stage of cartilage fish. Next, these isolated receptors were used to investigate hormone responsiveness in detail. As a result, we found some differences between cartilaginous fish receptors and human receptors, and then we identified the causative site. By analyzing the function of steroid receptors in cartilaginous fish in this way, we were able to obtain some findings that lead to the functional evolution of the receptors.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 19K06734
• Study of functional evolution of adrenal steroid receptor in evolutionary process
  Grants-in-Aid for Scientific Research
  2014 - 2016
  Katsu Yoshinao
  The adrenal steroid receptor binds to adrenal steroids such as glucocorticoids and mineralocorticoids secreted from the adrenal cortex and is involved in the mechanism of maintaining the homeostasis of animals and endocrine secretions. However, it is still unknown at which stage of biological evolution the mechanism of maintaining endocrine homeostasis by adrenal steroid receptors found in higher vertebrates such as humans. The purpose of this research project was to clarify the process of adrenal steroid receptor gene appearance and function acquisition in evolution process. As a result, ancient fishes, gar and sturgeon have the adrenal steroid receptor genes like humans, and the adrenal steroid receptors from ancient fishes have functionally equivalent to human receptors. These results can be expected to serve as important clues to elucidate the molecular evolution of the adrenal steroid receptor.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 26440159
• Elucidation of a gene duplication and the gain of function of the estrogen receptor during the evolution
  Grants-in-Aid for Scientific Research
  2011 - 2013
  KATSU Yoshinao
  The estrogen receptor interacts with estrogen which is female sex hormone, and participates in mechanism of the homeostatic maintenance of the vertebrates. However, it is yet unknown that the molecular evolution of estrogen receptor gene and protein. This research theme was carried out for the appearance of the estrogen receptor gene with the organic evolution and the elucidation of the process of the gain of function. As a result, it became clear that the elasmobranchii has the estrogen receptor genes that encode a functional receptor like higher vertebrates. Our functional analysis suggest that the function of estrogen receptor as a hormone-dependent transcription factor might be gain through the evolutionary process. The above-mentioned result will become the important clue in elucidating the molecular evolution of the estrogen receptor.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 23570067
• Basic study on the effect of endocrine disruptors on reptiles reproduction using a model of American alligators, Alligator Mississippiensis
  Grants-in-Aid for Scientific Research
  2009 - 2011
  OHTA Yasuhiko; KATSU Yoshinao; TAKEUCHI Takashi; IGUCHI Taisen
  In American alligator showing temperature-dependent sex determination(TSD), development of reproductive organs, ontogeny of expression of estrogen and progesteronereceptor and candidates involved in the TSD were identified during the thermo-sensitiveperiod. These results may contribute to the understanding of endocrine disrupters onreptiles.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Tottori University, 21510068
• 性ホルモン受容体の分子進化
  科学研究費補助金
  2008 - 2010
  性ホルモン受容体は、進化上いつから存在するのか、DNAとの結合能力やホルモンとの結合能力は、どの生物段階から備わったのかを調べる。
  Competitive research funding
• 爬虫類の性決定・性分化の分子機構解析
  科学研究費助成事業
  2005 - 2006
  勝 義直; 井口 泰泉
  爬虫類である全てのワニ類と大部分のカメ類の性決定は、環境要因(外気の温度)によって決定する事が分かっている。しかし、この性染色体によらない温度依存的性決定の分子機構については、ほとんどわかっていない。本研究は、この爬虫類の性決定・性分化の分子機構を解析することを目的として行なわれた。本年度は、温度と密接に関連する遺伝子の候補として、熱ショックタンパク類の関連遺伝子のクローニングを行なった。これまでの研究からも予想されたが、鳥類のHSPとの相同性が高いと言う事が判明した。さらに、ワニは初期発生の一定の時期(ステージ19から24まで)の温度が重要で、この時期に性が決定する事が分かっている。オスになる温度、メスになる温度でそれぞれ処理した初期胚から生殖腺を摘出し、今回得られたHSP群の発現パターンを調べたところ、いずれのHSPもすでにステージ19から発現している事がわかった。さらに、その発現量は発生にしたがって増減することはなく、ほぼ一定のままであった。また、オスとメスでの差は観察できなかった。この結果は、温度依存性の性決定機構をもつワニでは、その性決定にはHSPは関与しないのではないかということを示唆している。しかし、メスへの分化に必要と考えられているエストロゲン受容体のか活性化機構にはHSPが関連することも知られているので、今後、さらに局在などを調べ性決定とHSPの関連を詳細に調べる必要があると考えている。さらに、オスへの分化に必要だと考えられる、抗ミュラー管ホルモン(AMH)遺伝子の全長のクローニングに成功した。また転写調節領域の単離も完了しており、今後どのように温度からの刺激がどのようにAMHの発現調節に繋がっていくのかを解析していく予定である。
  日本学術振興会, 特定領域研究, 大学共同利用機関法人自然科学研究機構(共通施設), 17052032
• ミジンコ(Daphnia Magna)遺伝子の網羅的解析
  科学研究費助成事業
  2003 - 2003
  勝 義直; 井口 泰泉; 渡邉 肇
  動物プランクトンであるミジンコは生態系の中でももっとも下位に位置し、生態系において非常に重要な位置を占めている。またミジンコは、その生活環の全てを水中で過ごすことから、環境の指標としても重要な生物であり、長年、環境や毒性の評価などにおいて、世界中の研究室で利用されてきている。特に近年、地球環境の重要性が認識されるにつれ、環境指標の生物としての重要性を増してきている。
  ところが、ミジンコの重要性が認識されてきているにもかかわらず、その遺伝子情報は驚くほど乏しい。例えばNCBIのデータベースでは、Daphniaで登録されている遺伝子はわずか271遺伝子でその大半がリボソーマルRNAとヘモグロビン遺伝子であり、実際にアノーテーションされている遺伝子は数種類に過ぎない。様々な生物種のゲノムやEST情報が読まれているなかで、環境の指標として今後重要性を増して行くであろうミジンコにおけるこの遺伝子情報は皆無に近いといえる。
  そこで本研究では、ミジンコについての基本的な遺伝情報を取得することを目的として、まずEST解析を行い、データの収集と解析を行った。この際の非常に大きな特色は、通常単為生殖をしているために作出が困難なオスのミジンコについての解析も行う点であった。我々は今まで報告のなかった100%のオスを作出する条件を見出しており、この条件により処理したミジンコからライブラリーを構築し、その遺伝子情報を解析することにより、通常発現している遺伝子の概要を把握すると同時に、生殖や性差に関連した遺伝子情報も取得した。
  日本学術振興会, 特定領域研究, 岡崎国立共同研究機構, 15011259
• 魚類、両生類、哺乳類の不可逆化の臨界期探索
  科学研究費助成事業
  2002 - 2003
  井口 泰泉; 大迫 誠一郎; 勝 義直; 渡邉 肇
  工業化時代の始まりと共に環境に放出された化学物質は野生生物の健康に大きな脅威となっており、それは現在も続いている。今までの環境問題は、致死作用、ガン化あるいは奇形といった健康影響のみに焦点が当てられてきた.しかし、最近見出された多くの事例から、内分泌撹乱と言った今までにはなかった新たな観点からの研究が必要となってきている。
  特に環境中に放出されたダイオキシン,農薬,ポリカーボネートの原材料,界面活性剤をはじめとした化学物質がホルモンの受容体,特にエストロゲン受容体に結合することによって体内のエストロゲンと同じ作用を示し,野生動物種の性器異常,発生異常,個体数の減少,ヒトの乳癌、子宮内膜症、精巣癌の増加,精子数の減少を誘起している可能性が示唆された。欧米でこの問題に強く関心がもたれるようになったのは1990年代前半からで、日本では1997年になってからこの問題が広く取り上げられるようになった。以後、厚生省や環境庁を中心に、胎児を含めたヒトに対する内分泌撹乱物質の曝露状況調査が進められており、その結果、日本人の体内にも多くの内分泌撹乱物質が蓄積していることが判明してきた。そして環境中に放出された化学物質の多くが、ホルモン様あるいは抗ホルモン様に作用するという実験的な証拠、および野外での観察結果が蓄積されつつある。動物の生殖系の発達は内分泌撹乱物質の曝露によって大きな影響を受ける.野生動物の研究から、内分泌撹乱物質の曝露により、雌雄ともに生殖腺および生殖腺付属器官の発生、機能分化およびホルモンの代謝に影響が出ている。多くの野生動物種の生殖系で同様の異常が見られることから、ヒトに対する影響も懸念されている。
  本研究では、モデル動物としてマウスへの影響に関する研究だけでなく、内分泌撹乱物質が水系に入ることから、魚類・両生類の発生・生殖に対しても着目し解析を行った。これにより、内分泌撹乱物質を簡便に検出する系を確立し、発生・生殖に対する作用機構の解明を試みた。
  日本学術振興会, 特定領域研究, 岡崎国立共同研究機構, 14042266
• Developmental Effect of Endocrine Disruptors on Fish and Mice
  Grants-in-Aid for Scientific Research
  1999 - 2000
  IGUCHI Taisen; KATSU Yoshinao
  Bisphenol-A (BPA), an estrogenic chemical, was given to pregnant mice and Japanese monkey and studied transplacental transfer. BPA was foun in fetal brain, liver and other organs in 30 min in mice and 1 h in monkey suggesting that BPA can be easily cross the placenta. BPA and a synthetic estrogen, diethylstilbestrol (DES), were given to pregnant mice and studied fertility and various abnormalities in female offspring. DES induced sterility, polyovular follicles in ovary and persistent stratification of vaginal epithelium, but not BPA.Hoxa-9 and a-10 genes in Mullerian duct were downregulated by DES in the fetal period suggesting the close correlation to uterine changes in DES-exposed mice. In order to study low dose issue of BPA, 2 and 20μg/kg body weight of BPA and 0.02-2μg/kg of DES were given to day 10 to 17 of pregnancy. In 20μg BPA-and all DES-exposed female offspring showed significantly early vaginal opening and lower body weight as compared to controls. This results suggest that there is a low dose effect of BPA, however, the mechanism underlie is still unclear. Neonatal DES treatment induced hypospadias in female mice, fusion of urethra and vaginal lumen at lower position of vagina, where apoptosis was observed. The critical period in induction of hypospadias was 7 days after birth. Neonatally BPA (150μg) treated female mice showed persistent estrus, and ovary-independent vaginal changes.
  In order to study estrogenic agents on development of fish, Fundulus heteroclitus embryos were exposed to estradiol. Various malformations, including sex ratio change were induced by estradiol. Estrogen receptor α and β were cloned and ER expression during development were analysed. FTZ-F1 gene was also cloned from Fundulus. In zebrafish, gonad develops to ovary by ca 20 days after hatching then a half of fish develop testis from the ovary. During testis formation, apoptosis of oocytes occurred in the ovary.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), 11839022