Effects of neonatally administered chlorpromazine and reserpine on the responsiveness of rat hepatic drug-metabolising enzymes to testosterone in adult life.

The effects of neonatally administered chlorpromazine and reserpine on the response of rat hepatic drug-metabolising enzymes to testosterone in adult life have been investigated using the chlorinated cyclodiene substrate DME. Neonatal treatment with chlorpromazine and reserpine had effects on the metabolism of DME similar to, but not as pronounced as, those of castration when adult. The effects of adult castration of male rats on hepatic microsomal metabolism of DME were fully reversed by treatment with testosterone propionate, with metabolism being restored to that of a control intact male. However, testosterone propionate treatment of either intact or castrated adult males that had received neonatal reserpine or chlorpromazine did not restore levels of metabolism to those characteristic of control adult male rats. These results suggest that neonatally administered chlorpromazine and reserpine alter the sensitivity of hepatic drug-metabolising enzymes to the actions of testosterone in adult life.

Effects of hypophysectomy on sex differences in the induction and depression of hepatic drug-metabolizing enzymes in the rat.

The role of the pituitary gland in the effects of treatment with phenobarbital, methylcholanthrene and morphine on hepatic drug metabolism in adult male and adult female rats has been investigated. A marked sex difference in the effects of treatment with these three compounds on hepatic drug metabolizing enzymes in intact adult rats was observed. No sex differences in the effects of phenobarbital methylcholanthrene or morphine on hepatic drug metabolizing enzymes were observed after treatment of hypophysectomized adult male and hypophysectomized adult female rats. The results indicate that the pituitary gland plays an important role in the determination of sex differences in the response of hepatic drug metabolizing enzymes to inducing agents.

Inhibitory effects of centrally acting drugs on the neonatal imprinting of sex differences in the hepatic metabolism of a dimethylated epoxide in the rat.

The effects of the neonatal administration of reserpine, chlorpromazine, phenobarbitone and morphine on the development of sex differences in hepatic drug metabolism in the rat have been investigated. Treatment of neonatal male rats with reserpine or chlorpromazine for the first two weeks post-partum significantly inhibited the development of sex differences in drug metabolism in adult life. Similar treatment of neonatal female rats with reserpine or chlorpromazine had no effect on the development of hepatic drug metabolism in adulthood. Morphine or phenobarbitone treatment of neonatal rats of either sex had no effect on the development of sex differences in hepatic drug metabolism in adult life.

Neonatal imprinting of sex differences in the hepatic metabolism of a chlorinated cyclodiene by rat liver microsomes.

The effects of neonatal gonadectomy and the neonatal administration of steroid hormones on the development of sex differences in hepatic drug metabolism in the adult rat have been investigated. Castration of male rats at birth prevented the development of sex differences in metabolism in adult life. The effects of neonatal castration of male rats on the development of sex differences in adult life were reversed by treatment of the neonate with testosterone but not by estradiol or dihydrotestosterone treatment. Treatment of neonatal female rats with testosterone had no effect on the development of a feminine pattern of metabolism unless the ovaries were removed before puberty, suggesting that the effects of neonatal imprinting by testosterone can be repressed by the actions of the ovaries in adulthood.