title: Differential regulation of rat testicular 5alpha-reductase type 1 and 2 isoforms by testosterone and FSH.
abstract: Testosterone is metabolised to the more potent androgen, dihydrotestosterone, by the 5alpha-reductase (5alphaR) enzyme. We previously showed that 5alpha-reduced androgens are important for maintaining androgen action on rat spermatogenesis when testicular testosterone concentrations are reduced. This study investigated expression and activity of the 5alphaR isoforms, type 1 (5alphaR-1) and type 2 (5alphaR-2), in the rat during hormone manipulation in order to understand the factors that regulate the testicular concentration of 5alphaR and testicular 5alpha-reduced androgen biosynthesis. Testicular 5alphaR-1 and 5alphaR-2 mRNA and enzyme activity were measured by real-time PCR and specific enzyme assays respectively. Hormone levels were first suppressed using two models of gonadotrophin suppression: testosterone and oestradiol treatment (LH/testosterone deficiency) or GnRH immunisation (LH/testosterone and FSH deficiency). Hormones were then either restored or suppressed for 6 days by a variety of hormonal treatments. 5alphaR-1 mRNA and enzyme activity increased when testosterone was suppressed, yet restoration of testosterone decreased 5alphaR-1 mRNA and enzyme activity, suggesting that testosterone negatively regulates 5alphaR-1. suppression of FSH decreased 5alphaR-1 mRNA yet FSH administration increased 5alphaR-1 mRNA, but no changes in 5alphaR-1 activity were observed within the 6 day period. In contrast to 5alphaR-1, testosterone did not affect the testicular concentration of 5alphaR-2 mRNA or activity, but there was evidence for modulation of 5alphaR-2 activity by FSH. Measurement of testicular androgens revealed that 5alphaR-1 was primarily responsible for the production of 5alpha-reduced metabolites. It is concluded that the 5alphaR isoforms in rat testis are differentially regulated by testosterone and FSH: testosterone negatively regulated 5alphaR-1 mRNA and enzyme activity but had no affect on 5alphaR-2, whereas FSH positively regulated 5alphaR-1 mRNA and appeared to regulate 5alphaR-2.
authors.affiliation: Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Pratis
authors.forename: L
authors.initials: L
authors.lastname: O'Donnell
authors.forename: G T
authors.initials: GT
authors.lastname: Ooi
authors.forename: P G
authors.initials: PG
authors.lastname: Stanton
authors.forename: R I
authors.initials: RI
authors.lastname: McLachlan
authors.forename: D M
authors.initials: DM
authors.lastname: Robertson
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D013196:Dihydrotestosterone / Q000378:metabolism; D004343:Drug Implants; D004958:Estradiol / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000276:immunology / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology / Q000494:pharmacology; D007106:Immune Sera / Q000494:pharmacology; D007114:Immunization; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000201:enzymology*; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000726:Androgen Antagonists; D004343:Drug Implants; D007106:Immune Sera; D007527:Isoenzymes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D005485:Flutamide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase