Effect of the anterior pituitary gland and gonads on enzyme components of the hepatic microsomal cytochrome P-450 system of male and female rats.

Abstract

The concentration of cytochrome P-450 in microsomes prepared from the livers of mature female Wistar-derived rats was significantly lower than in mature males. This sex difference was abolished after hypophysectomy, when the concentration of the cytochrome in males and females was not significantly different from that in the intact male. A concentration of cytochrome P-450 characteristic of females was restored by two anterior pituitary transplants under the kidney capsule of hypophysectomized females; a partial 'feminization' occurred in similarly treated hypophysectomized males. A partial 'feminization' was also achieved by the administration of rat or sheep prolactin to hypophysectomized females. Unexpectedly, the administration of l-dihydroxyphenylalanine to normal females was without effect on cytochrome P-450, whereas in intact males 'feminization' resulted. Castration of adult rats resulted in the 'feminization' of cytochrome P-450, whereas ovariectomy was without effect. Administration of testosterone propionate for 10 days, either immediately after the operation or 14 weeks later to rats castrated when adult failed, however, to reverse the fall in cytochrome P-450. The establishment of a higher concentration of cytochrome P-450 in the liver of female rats could not be brought about by the administration of testosterone propionate, whether given as a single dose on the second day after birth or as a 10-day course of treatment after puberty or both. It is concluded that the sex difference in hepatic microsomal cytochrome P-450 is maintained by the release in the female of an anterior pituitary factor(s) that serves to depress its concentration. The factor(s) shows some of the characteristics of prolactin but the findings are not consistent with that hormone being responsible for all of the effects observed. The release of the factor(s) in the male may be inhibited by a compound of gonadal origin other than testosterone. A sex difference could not be 'imprinted' in the female by either neonatal and/or postpubertal testosterone treatment. The concentration of hepatic microsomal cytochrome b5 and the specific activity of NADPH-cytochrome c reductase were found not to be sex-dependent in the rats used. However, anterior pituitary factor(s) other than prolactin and growth hormone act to suppress partially the concentration of the former and to promote the specific activity of the latter in the endoplasmic reticulum of rat hepatocytes.