The Development of a Male Pseudohermaphroditic Rat Using an Inhibitor of the Enzyme 5α-Reductase*

Publisher Website
Google Scholar
Abstract
Incomplete masculinization of the external genitalia occurred in male Sprague-Dawley rats treated with a potent inhibitor of enzyme 5.alpha.-reductase at the critical period of sexual differentiation in utero. The studies were performed using the 5.alpha.-reductase inhibitor, 4-methyl-4-aza-5-pregnan-3-one-20[s] carboxylate, 1 of a series of aza steroids known to competitively inhibit the enzyme 5.alpha.-reductase. The degree of inhibition of male external genital development was dependent upon the dose of the inhibitor; at a dose of 36 mg/kg .cntdot. day, there was complete feminization of the external genitalia of the male animal with a urogenital sinus and a pseudovagina. Apparently, 5.alpha.-reductase activity and dihydrotestosterone (17.beta.-hydroxy-5.alpha.-androstan-3-one) formation are essential for normal differentiation of male external genitalia. Epididymis, vasa deferentia and seminal vesicles wee present at all doses of the inhibitor, suggesting testosterone dependency. Confirmation of the testosterone dependency of Wolffian ductal differentiation awaits further studies, particularly comparison studies with the rabbit and dog, since Wolffian ductal differentiation in the rat, unlike the rabbit and dog, is not abolished with the antiandrogen, cyproterone acetate. The presence of prostatic buds, despite complete external genital feminization, was unexpected and suggests that these structures may have different thresholds of response for dihydrotestosterone. Prostatic differentiation may have a much lower threshold, requiring less dihydrotestosterone for differentiation.

This publication has 1 reference indexed in Scilit: