The Effect of in Vitro Androgen Stimulation Upon Androgen Metabolism and Trophic Parameters in Cultured Human Epididymis/Der Einfluß der in vitro-Stimulation auf den Androgenstoffwechsel und die trophischen Parameter auf die Nebenhodenkultur des Menschen

Previous work has clearly demonstrated that inhibition of 5 alpha-dihydrotestosterone (DHT) formation in vivo is not as effective as total androgen ablation (castration) in causing involution of the prostate. It is likely that this is due to the fact that testosterone is partially effective in maintaining androgen action. To provide insight into this observation, the androgenic metabolites of testosterone, androstenedione, and 5 alpha-DHT, were measured in prostate tissue and in blood of 5 alpha-reductase inhibitor (finasteride)-treated adult male rats. Finasteride treatment caused a significant decrease in prostatic DHT levels and a profound increase in prostatic testosterone and androstenedione levels. Similarly, circulating DHT levels were decreased in finasteride-treated rats (0.02 ng/ml compared with 0.05 ng/ml seen in control rats); and circulating androstenedione and testosterone levels were significantly elevated in finasteride-treated animals compared with controls. The in vitro effects of finasteride were assessed on the metabolism of [3H]testosterone in a tissue-slice assays. In the prostate, the inhibition of 5 alpha-reductase activity resulted not only in the decreased formation of 5 alpha-reduced metabolites (primarily DHT and 5 alpha-androstanedione), but also an increase in the 17-oxo metabolite androstenedione. In contrast, the tissues derived from the embryonic wolffian duct (seminal vesicle and epididymis) formed relatively low amounts of 17-keto steroids. Because DHT is a high affinity ligand for the androgen receptor and androstenedione shows very little, if any, affinity for the receptor, these studies suggest that 5 alpha-reduction of testosterone may be a mechanism to amplify androgen action in urogenital tissues such as the prostate by preventing catabolism of testosterone to the inactive androgen, androstenedione, at the site of hormone action.

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Androgen Metabolism in the Prostate of the Finasteride-Treated, Adult Rat: A Possible Explanation for the Differential Action of Testosterone and 5α-Dihydrotestosterone during Development of the Male Urogenital Tract¹

George

1997

Endocrinology

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The Effect of in Vitro Androgen Stimulation Upon Androgen Metabolism and Trophic Parameters in Cultured Human Epididymis/Der Einfluß der in vitro-Stimulation auf den Androgenstoffwechsel und die trophischen Parameter auf die Nebenhodenkultur des Menschen

Cited by 1 publication

References 22 publications

Androgen Metabolism in the Prostate of the Finasteride-Treated, Adult Rat: A Possible Explanation for the Differential Action of Testosterone and 5α-Dihydrotestosterone during Development of the Male Urogenital Tract¹

Androgen Metabolism in the Prostate of the Finasteride-Treated, Adult Rat: A Possible Explanation for the Differential Action of Testosterone and 5α-Dihydrotestosterone during Development of the Male Urogenital Tract¹

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The Effect of in Vitro Androgen Stimulation Upon Androgen Metabolism and Trophic Parameters in Cultured Human Epididymis/Der Einfluß der in vitro-Stimulation auf den Androgenstoffwechsel und die trophischen Parameter auf die Nebenhodenkultur des Menschen

Cited by 1 publication

References 22 publications

Androgen Metabolism in the Prostate of the Finasteride-Treated, Adult Rat: A Possible Explanation for the Differential Action of Testosterone and 5α-Dihydrotestosterone during Development of the Male Urogenital Tract1

Androgen Metabolism in the Prostate of the Finasteride-Treated, Adult Rat: A Possible Explanation for the Differential Action of Testosterone and 5α-Dihydrotestosterone during Development of the Male Urogenital Tract1

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Androgen Metabolism in the Prostate of the Finasteride-Treated, Adult Rat: A Possible Explanation for the Differential Action of Testosterone and 5α-Dihydrotestosterone during Development of the Male Urogenital Tract¹

Androgen Metabolism in the Prostate of the Finasteride-Treated, Adult Rat: A Possible Explanation for the Differential Action of Testosterone and 5α-Dihydrotestosterone during Development of the Male Urogenital Tract¹