title: 5alpha-androstane-3alpha,17beta-diol is formed in tammar wallaby pouch young testes by a pathway involving 5alpha-pregnane-3alpha,17alpha-diol-20-one as a key intermediate.
abstract: The synthetic pathway by which 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol) is formed in the testes of tammar wallaby pouch young was investigated by incubating testes from d 20-40 males with various radioactive precursors and analyzing the metabolites by thin-layer chromatography and HPLC. [(3)H]Progesterone was converted to 17-hydroxyprogesterone, which was converted to 5alpha-adiol by two pathways: One involves the formation of testosterone and dihydrotestosterone as intermediates, and the other involves formation of 5alpha-pregnane-3alpha,17alpha-diol-20-one (5alpha-pdiol) and androsterone as intermediates. Formation of 5alpha-adiol from both [(3)H]testosterone and [(3)H]progesterone was blocked by the 5alpha-reductase inhibitor 4MA. The addition of nonradioactive 5alpha-pdiol blocked the conversion of [(3)H]progesterone to 5alpha-adiol, and [(3)H]5alpha-pdiol was efficiently converted to androsterone and 5alpha-adiol. We conclude that expression of steroid 5alpha-reductase in the developing wallaby testes allows formation of 5alpha-reduced androgens by a pathway that does not involve testosterone as an intermediate.
authors.affiliation: Department of Zoology, University of Melbourne, Victoria 3010, Australia. jwils1@mednet.swmed.edu
authors.forename: Jean D
authors.initials: JD
authors.lastname: Wilson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Auchus
authors.forename: Michael W
authors.initials: MW
authors.lastname: Leihy
authors.forename: Oleg L
authors.initials: OL
authors.lastname: Guryev
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Estabrook
authors.forename: Susan M
authors.initials: SM
authors.lastname: Osborn
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Shaw
authors.forename: Marilyn B
authors.initials: MB
authors.lastname: Renfree
mesh_terms: D000367:Age Factors; D015113:Androstane-3,17-diol / Q000096:biosynthesis*; D000818:Animals; D005260:Female; D007614:Macropodidae / Q000378:metabolism*; D008297:Male; D011276:Pregnanediol / Q000031:analogs & derivatives / Q000378:metabolism*; D011372:Progestins / Q000493:pharmacokinetics; D013737:Testis / Q000254:growth & development / Q000378:metabolism*; D013739:Testosterone / Q000493:pharmacokinetics; D014316:Tritium
chemical_list: D011372:Progestins; D014316:Tritium; D015113:Androstane-3,17-diol; D013739:Testosterone; D011276:Pregnanediol