Kramer R E, Greiner J W, Rumbaugh R C, Sweeney T D, Colby H D
J Pharmacol Exp Ther. 1979 Jan;208(1):19-23.
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.
以往的研究已经证明垂体在肝脏药物和类固醇代谢调节中起重要作用。本研究旨在确定垂体与性腺激素对大鼠肝脏药物代谢作用之间的关系。给去势雄性大鼠注射睾酮可增加肝脏微粒体细胞色素P - 450浓度，并提高乙基吗啡脱甲基化和苯并(a)芘羟基化的速率。另一方面，雌二醇处理可降低去势大鼠的细胞色素P - 450水平，并降低苯胺、乙基吗啡和苯并(a)芘的代谢速率。然而，当给予垂体切除的雄性大鼠时，睾酮和雌二醇均不影响细胞色素P - 450水平或酶活性。同样，仅在垂体存在的情况下，给予5α - 二氢睾酮才会增加肝脏药物代谢。在没有甲状腺或肾上腺的情况下，睾酮和雌二醇的作用均能完全表现出来，排除了对任一器官的需求。结果表明，性腺激素（睾酮和雌二醇）对肝脏混合功能氧化酶的作用绝对依赖于垂体。
