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Role of the Alternate Pathway of Dihydrotestosterone Formation in Virilization of the Wolffian Ducts of the Tammar Wallaby, Macropus eugenii

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

Address all correspondence and requests for reprints to: Geoff Shaw, Department of Zoology, The University of Melbourne, Victoria 3010, Australia. E-mail: g.shaw{at}zoology.unimelb.edu.au.

Dihydrotestosterone in androgen target tissues is formed under most circumstances by the 5-reduction of testosterone, but an alternate pathway involves the oxidation of androstanediol to dihydrotestosterone. To investigate the mechanism by which androgens virilize the Wolffian ducts in the tammar wallaby, [³H]progesterone was incubated with testes from d 10 and 19 pouch young, and radioactivity was recovered in testosterone and androstanediol at both ages. Analysis of the intermediates indicates that androstanediol was formed both from testosterone via 5-reduction and 3-keto reduction and directly from 5-reduced progestogens. 5-Reductase activity was high in minces of mesonephros/epididymis from d 6–21 pouch young. When minces of urogenital tract tissues from d 19 pouch young were incubated with [³H]testosterone, [³H]dihydrotestosterone, and [³H]androstanediol, dihydrotestosterone was the principal androgen formed in the mesonephros/epididymis, urogenital sinus, and urogenital tubercle, whereas androstanediol was the principal androgen formed by the testis. In intact pouch young studied between d 10 and 34, administration of the 5-reductase inhibitor, 17ß-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5-androstan-3-one, blocked virilization of the Wolffian ducts in males, and administration of androstanediol caused virilization of the Wolffian ducts in females. We conclude that dihydrotestosterone, largely formed in the tissue by the oxidation of androstanediol derived from the testes and also the 5-reduction of testosterone, is responsible for Wolffian duct virilization in this species.