Steroid 5alpha-reductase 1 promotes 5alpha-androstane-3alpha,17beta-diol synthesis in immature mouse testes by two pathways.
5alpha-Androstane-3alpha,17beta-diol (androstanediol) is the predominant androgen in immature mouse testes, and studies were designed to investigate its pathway of synthesis, the steroid 5alpha-reductase isoenzyme involved in its formation, and whether testicular androstanediol is formed in embryonic mouse testes at the time of male phenotypic development. In 24-26-day-old immature testes, androstanediol is formed by two pathways; the predominant one involves testosterone --> dihydrotestosterone --> androstanediol, and a second utilizes the pathway progesterone --> 5alpha-dihydroprogesterone --> 5alpha-pregnane-3alpha-ol-20-one --> 5alpha-pregnane-3alpha,17alpha-diol-20-one --> androsterone --> androstanediol. Formation of androstanediol was normal in testes from mice deficient in steroid 5alpha-reductase 2 but absent in testes from mice deficient in steroid 5alpha-reductase 1, indicating that isoenzyme 2 is not expressed in day 24-26 testes. The fact that androstenedione and testosterone were the only androgens identified after incubation of day 16 and 17 embryonic testes with [3H]progesterone implies that androstanediol formation in the testis plays no role in male phenotypic differentiation in the mouse.
Mahendroo
Mala
M
Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032, USA.
Wilson
Jean D
JD
Richardson
James A
JA
Auchus
Richard J
RJ
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000502:physiology*; D045930:Anabolic Agents / Q000378:metabolism*; D015113:Androstane-3,17-diol / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D005260:Female; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011374:Progesterone / Q000378:metabolism; D015398:Signal Transduction; D013737:Testis / Q000196:embryology* / Q000201:enzymology*; D013739:Testosterone / Q000378:metabolism
D045930:Anabolic Agents; D007527:Isoenzymes; D015113:Androstane-3,17-diol; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase