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Endocrinology Vol. 144, No. 2 575-580
Copyright © 2003 by The Endocrine Society

ARTICLE

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

Jean D. Wilson, Richard J. Auchus, Michael W. Leihy, Oleg L. Guryev, Ronald W. Estabrook, Susan M. Osborn, Geoffrey Shaw and Marilyn B. Renfree

Department of Zoology (J.D.W., M.W.L., S.M.O., G.S., M.B.R.), University of Melbourne, Victoria 3010, Australia; and Departments of Internal Medicine (J.D.W., R.J.A.) and Biochemistry (O.L.G., R.W.E.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-8857

Address all correspondence and requests for reprints to: Jean D. Wilson, M.D., 5323 Harry Hines Boulevard, Dallas, Texas 75390-8857. E-mail: jwils1{at}mednet.swmed.edu.

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




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