Requirement of the pituitary gland for gonadal hormone effects on hepatic drug metabolism in rats.

Previous studies have demonstrated an important role for the pituitary gland in the regulation of hepatic drug and steroid metabolism. The present studies were carried out to determine the relationship between the pituitary gland and the actions of gonadal hormones on hepatic drug metabolism in rats. Testosterone administration to castrated male rats increased hepatic microsomal cytochrome P-450 concentrations and enhanced the rates of ethylmorphine demethylation and benzo(a)pyrene hydroxylation. Estradiol treatment, on the other hand, lowered cytochrome P-450 levels and decreased the rates of aniline, ethylmorphine and benzo(a)pyrene metabolism in orchiectomized rats. However, when given to hypophysectomized male rats, neither testosterone nor estradiol affected cytochrome P-450 levels or enzyme activities. Similarly, 5alpha-dihydrotestosterone administration increased hepatic drug metabolism only in the presence of the pituitary gland. The effects of both testosterone and estradiol were fully demonstrable in the absence of the thyroid or adrenal glands, excluding the need for either organ. The results indicate an absolute dependence on the pituitary gland for gonadal hormone (testosterone and estradiol) actions on hepatic mixed-function oxidases.