SEX-DIFFERENCES IN PITUITARY-GONADAL REGULATION OF HEPATIC 5-ALPHA-REDUCTASE AND 16-ALPHA-HYDROXYLASE

In an effort to more fully understand the mechanisms which regulate 5α-reductase and 16α-hydroxylase. these studies have examined the effects of prepubertal hypophysectomy (HYPOX) on day 21, castration (CASTR) on day 42, or HYPOX (day 21) + CASTR (day 42) on adult (day 65) hepatic enzyme activity and enzyme modulation (responsiveness) by postpubertal hormone administration. In intact adult rats, hepatic -5α-reductase is significantly higher in females compared to males whereas 16α-hydroxylase is significantly higher in male livers. Castration results in a feminization of both 5α-reductase (increase) and 16α-hydroxylase (decrease) in the male rat, but has no effect in the female rat. HYPOX or HYPOXCASTR virtually abolishes 5α-reductase in both sexes; 16α-hydroxylase is also significantly decreased in male rats following HYPOX or HYPOX-CASTR. Conversely. HYPOX or HYPOX-CASTR of the female rat results in an elevation of 16α-hydroxylase. Female enzyme activities are unresponsive to the designated hormone treatment regardless of the surgical (endocrine) status of the animal. In contrast, estradiol-17β (E2) treatment feminizes both 16α-hydroxylase (decrease) and 5α-reductase (increase) in the intact male rat. while testosterone propionate (TP) treatment masculinizes (increased 16α-hydroxylase and decreased 5α-reductase activity) both enzymes in the castrate male rat. Enzyme levels are unaltered by hormone treatment in the absence of the pituitary. These studies indicate that hepatic 16α-hydroxylase and 5α-reductase are modulated by E2 and TP in the male rat. whereas equivalent doses do not change enzyme activities in female rats. These findings also suggest sex-dependent differences in sensitivity and/or regulatory mechanisms of these enzymes. © 1979.