The role of neonatal and pubertal gonadal hormones in regulating the sex dependence of the hepatic microsomal testosterone 5-reductase activity in the rat

Abstract

ABSTRACT Hepatic microsomal testosterone 5-reductase activity was approximately fourfold higher in adult female rats than in males. This discrepancy was only partly androgen-dependent since gonadectomy of male rats at 68 days of age resulted in only a partial increase of the enzyme activity. This increase was reversible by the administration of testosterone. Similar treatment, however, produced no effect in the female rat, indicating that there is a sex difference in testosterone responsivity. Castration of newborn male rats resulted in a marked increase in the basal enzyme activity. This increase was not affected by treating the adults with testosterone. Giving testosterone to male rats immediately after neonatal gonadectomy, or to newborn female rats, did not produce the male pattern of both the basal enzyme activity and the testosterone responsivity in adulthood. These results suggest that a brief exposure to neonatal androgen is not critical for the expression of the male type of enzyme activity, but that the continuous presence of the male gonads up to and including the pubertal period is essential. Exposure of pubescent female rats to testosterone during the period from 35 to 50 days of age resulted in a significant increase in testosterone sensitivity when tested at 90 days of age, suggesting that pubertal exposure to androgen is important for the expression of testosterone responsivity in adulthood. The sensitivity was potentiated when the animals were ovariectomized before puberty. Furthermore, the enzyme activity in prepubertally ovariectomized female rats was significantly lower than that in adult gonadectomized animals. The decreased level of activity returned to the control value when oestrogen was replaced during puberty, indicating that peripubertal oestrogen exposure is required for maintaining the high level of activity found in adult female rats. The present findings suggest that the pubertal period represents a sensitive phase during which sex hormones act to regulate the sexual differentiation of testosterone 5-reductase activity in the rat. J. Endocr. (1985) 106, 71–79