Rumbaugh R C, Colby H D
Endocrinology. 1980 Sep;107(3):719-24. doi: 10.1210/endo-107-3-719.
Previous studies have established that the effects of estradiol (E2) on hepatic steroid and drug metabolism are demonstrable only in the presence of the pituitary gland. Studies were carried out to test the hypothesis that GH is the pituitary feminizing factor mediating the actions of E2 on hepatic metabolism. E2 and GH administered to castrated male rats had similar effects on hepatic enzymes, decreasing the oxidataive metabolism of drugs [ethylmorphine demethylation, aniline, hydroxylation, and benzo(a)pyrene hydroxylation) and increasing steroid (corticosterone) delta 4-hydrogenase activity. None of these effects of E2 or GH could be demonstrated in hypophysectomized (hypox) rats. However, GH administration to T4- or ACTH-treated hypox rats resulted in some of the changes in drug and steroid metabolism seen in animals with intact pituitary glands. The actions of GH on hepatic microsomal enzymes were fully demonstrable in hypox rats receiving both T4 and ACTH. E2 had no effects in T4 plus ACTH-treated hypox rats. These and prior observations are consistent with the hypothesis that GH mediates the actions of E2 on hepatic microsomal drug- and steroid-metabolizing enzymes. The data also indicates that the cations of GH on hepatic metabolism are dependent upon the interactions with still other endocrine factors.
以往的研究已证实，雌二醇（E2）对肝脏类固醇和药物代谢的影响只有在垂体存在的情况下才能显现出来。开展了多项研究以验证生长激素（GH）是介导E2对肝脏代谢作用的垂体雌性化因子这一假说。给去势雄鼠注射E2和GH，对肝脏酶产生了相似的影响，降低了药物的氧化代谢（乙基吗啡去甲基化、苯胺、羟基化以及苯并[a]芘羟基化），并增加了类固醇（皮质酮）δ4-脱氢酶活性。在垂体切除的（垂体切除的）大鼠中，无法证实E2或GH的这些作用。然而，给接受T4或促肾上腺皮质激素（ACTH）治疗的垂体切除大鼠注射GH，会导致在垂体完整的动物身上出现一些药物和类固醇代谢的变化。在同时接受T4和ACTH的垂体切除大鼠中，GH对肝脏微粒体酶的作用得到了充分证实。E2对接受T4加ACTH治疗的垂体切除大鼠没有影响。这些以及之前的观察结果与GH介导E2对肝脏微粒体药物和类固醇代谢酶作用的假说一致。数据还表明，GH对肝脏代谢的作用取决于与其他内分泌因子的相互作用。
