Analyses of Molecular Characteristics and Enzymatic Activities of Ovine HSD17B3
Mohammad Sayful Islam,
Junsuke Uwada,
Junki Hayashi,
Kei-ichiro Kikuya,
Yuki Muranishi,
Hiroyuki Watanabe,
Kazuhide Yaegashi,
Kazuya Hasegawa,
Takanori Ida,
Takahiro Sato,
Yoshitaka Imamichi,
Takeshi Kitano,
Yoshimichi Miyashiro,
Rafiqul Islam Khan,
Satoru Takahashi,
Akihiro Umezawa,
Nobuo Suzuki,
Toshio Sekiguchi,
Takashi Yazawa
Affiliations
Mohammad Sayful Islam
Department of Biochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan
Junsuke Uwada
Department of Biochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan
Junki Hayashi
Department of Biochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan
Kei-ichiro Kikuya
Department of Biochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan
Yuki Muranishi
Department of Life and Food Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
Hiroyuki Watanabe
Department of Life and Food Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
Kazuhide Yaegashi
Animal Lab Ltd., Asahikawa 070-8012, Japan
Kazuya Hasegawa
Faculty of Health and Medical Science, Teikyo Heisei University, Tokyo 170-8445, Japan
Takanori Ida
Center for Animal Disease Control, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
Takahiro Sato
Division of Molecular Genetics, Institute of Life Sciences, Kurume University, Fukuoka 830-0011, Japan
Yoshitaka Imamichi
Department of Marine Bioscience, Faculty of Marine Bioscience, Fukui Prefectural University, Fukui 917-0003, Japan
Takeshi Kitano
Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan
Yoshimichi Miyashiro
ASKA Pharma Medical Co., Ltd., Kawasaki 251-8555, Japan
Rafiqul Islam Khan
Department of Biochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan
Satoru Takahashi
Department of Pediatrics, Asahikawa Medical University, Asahikawa 078-8510, Japan
Akihiro Umezawa
Department of Reproduction, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
Nobuo Suzuki
Noto Marine Laboratory, Division of Marine Environmental Studies, Institute of Nature and Environmental Technology, Kanazawa University, Kanazawa 927-0553, Japan
Toshio Sekiguchi
Noto Marine Laboratory, Division of Marine Environmental Studies, Institute of Nature and Environmental Technology, Kanazawa University, Kanazawa 927-0553, Japan
Takashi Yazawa
Department of Biochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan
17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) converts androstenedione (A4) into testosterone (T), which regulates sex steroid production. Because various mutations of the HSD17B3 gene cause disorder of sex differentiation (DSD) in multiple mammalian species, it is very important to reveal the molecular characteristics of this gene in various species. Here, we revealed the open reading frame of the ovine HSD17B3 gene. Enzymatic activities of ovine HSD17B3 and HSD17B1 for converting A4 to T were detected using ovine androgen receptor-mediated transactivation in reporter assays. Although HSD17B3 also converted estrone to estradiol, this activity was much weaker than those of HSD17B1. Although ovine HSD17B3 has an amino acid sequence that is conserved compared with other mammalian species, it possesses two amino acid substitutions that are consistent with the reported variants of human HSD17B3. Substitutions of these amino acids in ovine HSD17B3 for those in human did not affect the enzymatic activities. However, enzymatic activities declined upon missense mutations of the HSD17B3 gene associated with 46,XY DSD, affecting amino acids that are conserved between these two species. The present study provides basic information and tools to investigate the molecular mechanisms behind DSD not only in ovine, but also in various mammalian species.
