title: Cyp11b1 is induced in the murine gonad by luteinizing hormone/human chorionic gonadotropin and involved in the production of 11-ketotestosterone, a major fish androgen: conservation and evolution of the androgen metabolic pathway.
abstract: We have shown previously that Cyp11b1, an 11beta-hydroxylase responsible for glucocorticoid biosynthesis in the adrenal gland, was induced by cAMP in androgen-producing Leydig-like cells derived from mesenchymal stem cells. We found that Cyp11b1 was induced in male Leydig cells, or female theca cells, when human chorionic gonadotropin was administered in immature mice. Expression of Cyp11b1 in rodent gonads caused the production of 11-ketotestosterone (11-KT), a major fish androgen, which induces male differentiation or spermatogenesis in fish. As in teleosts, plasma concentrations of 11-KT were elevated in human chorionic gonadotropin-treated mice. In contrast to teleosts, however, plasma concentrations of 11-KT were similar in both sexes, despite levels of testosterone, a precursor substrate, being about 20 times higher in male mice. Because expression of 11beta-hydroxysteroid dehydrogenase type 2, was much higher in the mouse ovary than in the testis, conversion of testosterone into 11-KT may occur more efficiently in the ovary. In a luciferase reporter system that was responsive to and activated by androgens, 11-KT efficiently activated mammalian androgen receptor-mediated transactivation. Our results suggest that the androgen metabolic pathway is conserved between teleosts and mammals, despite sexual dominance and reproductive functions of 11-KT being altered during evolution.
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Shimoaizuki, Matsuoka, Eiheiji-cho, Fukui, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yazawa
authors.forename: Miki
authors.initials: M
authors.lastname: Uesaka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Inaoka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizutani
authors.forename: Toshio
authors.initials: T
authors.lastname: Sekiguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kajitani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kitano
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000502:physiology; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D005075:Biological Evolution; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004790:Enzyme Induction; D006066:Gonads / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011944:Receptors, Androgen / Q000378:metabolism; D013252:Steroid 11-beta-Hydroxylase / Q000096:biosynthesis*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000096:biosynthesis
chemical_list: D000728:Androgens; D006063:Chorionic Gonadotropin; D011944:Receptors, Androgen; D013739:Testosterone; D007986:Luteinizing Hormone; D042842:11-beta-Hydroxysteroid Dehydrogenases; D013252:Steroid 11-beta-Hydroxylase; C003600:11-ketotestosterone