Neonatal treatment with testosterone proprionate or diethylstilbestrol alters sex differentiation of 5α-reductase and 16α-hydroxylase

Abstract

Neonatal exposure to testosterone appears to determine the normal programming of certain hepatic enzyme activities, perhaps via the aromatization of testosterone to estrogens in the brain. These studies examine whether neonatal exposure to testosterone propionate (TP) or diethylstilbestrol (DES) alters the normal programming of hepatic 16α-hydroxylase (using [4- 14C]-androstenedione as substrate) or 5α-reductase (using [4- 14C]-testosterone as substrate). In normal adult rats, 16α-hydroxylase is higher in male liver, while 5α-reductase is higher in female liver. Neonatal administration of TP or DES to intact animals produce decreases in adult male 16α-hydroxylase (feminization). Levels of 16α-hydroxylase in resultant adult females and 5α-reductase activity levels in adult male and female rats were unaffected by neonatal TP or DES treatment. Treatment of neonatal rats with DES but not TP results in significantly reduced circulating androgen levels. Therefore, feminized levels of 16α-hydroxylase do not correlate with serum androgen levels. Neonatal castration of male rats on day 1 results in feminization of 16α-hydroxylase and 5α-reductase activities in adult animals. TP or DES treatment on day 2 did not reverse the effect of neonatal castration. These studies demonstrate that the hormonal regulation of the hepatic steroid metabolizing enzymes, 5α-reductase and 16α-hydroxylase, is different. 16α-hydroxylase appears to be more sensitive to neonatal hormonal modulation than is 5α-reductase.