5α-Androstane-3α,17β-Diol Is Formed in Tammar Wallaby Pouch Young Testes by a Pathway Involving 5α-Pregnane-3α,17α-Diol-20-One as a Key Intermediate

Author:

Wilson Jean D.12,Auchus Richard J.2,Leihy Michael W.1,Guryev Oleg L.3,Estabrook Ronald W.3,Osborn Susan M.1,Shaw Geoffrey1,Renfree Marilyn B.1

Affiliation:

1. Department of Zoology (J.D.W., M.W.L., S.M.O., G.S., M.B.R.), University of Melbourne, Victoria 3010, Australia;

2. Departments of Internal Medicine (J.D.W., R.J.A.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-8857

3. Biochemistry (O.L.G., R.W.E.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-8857

Abstract

The synthetic pathway by which 5α-androstane-3α,17β-diol (5α-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. [3H]Progesterone was converted to 17-hydroxyprogesterone, which was converted to 5α-adiol by two pathways: One involves the formation of testosterone and dihydrotestosterone as intermediates, and the other involves formation of 5α-pregnane-3α,17α-diol-20-one (5α-pdiol) and androsterone as intermediates. Formation of 5α-adiol from both [3H]testosterone and [3H]progesterone was blocked by the 5α-reductase inhibitor 4MA. The addition of nonradioactive 5α-pdiol blocked the conversion of [3H]progesterone to 5α-adiol, and [3H]5α-pdiol was efficiently converted to androsterone and 5α-adiol. We conclude that expression of steroid 5α-reductase in the developing wallaby testes allows formation of 5α-reduced androgens by a pathway that does not involve testosterone as an intermediate.

Publisher

The Endocrine Society

Subject

Endocrinology

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