Barouki R, Perrot N, Bouguet J, Chobert M N, Toffis V, Pavé-Preux M, Yang C S, Beaune P, Hanoune J
INSERM U-99, hôpital Henri Mondor, Créteil, France.
Biochem Pharmacol. 1989 Feb 15;38(4):677-84. doi: 10.1016/0006-2952(89)90215-3.
The increase in serum gamma-glutamyl transpeptidase (GGT) is a well known marker of chronic alcoholism in man. We have previously shown that ethanol (180 mM) induces GGT activity 2-3-fold in the C2 rat hepatoma cell line. In this study, we have analyzed the interaction of ethanol with steroid hormones and drugs in this well defined cell culture system. Dexamethasone (100 nM), a synthetic glucocorticoid agonist, completely prevented the induction of GGT by ethanol, but had no effect when added alone. This inhibitory effect was also observed with other corticosteroids, but not with sex steroids; it was prevented by RU 486, a glucocorticoid antagonist. These observations suggest that dexamethasone acts through a high affinity glucocorticoid receptor. Conversely, ethanol did not interfere with the glucocorticoid induction of alanine aminotransferase in the same cell. We have analyzed the metabolism of ethanol in the C2 cells. These cells lack significant alcohol dehydrogenase activity as well as any cytochrome P-450 Alc immunoreactivity. Dexamethasone did not modify the disappearance of ethanol in the culture medium of those cells. We conclude that glucocorticoid hormones interact with ethanol at the cellular level, and that this interaction does not involve a modification of alcohol metabolism.
血清γ-谷氨酰转肽酶（GGT）升高是人类慢性酒精中毒的一个众所周知的标志物。我们之前已经表明，乙醇（180 mM）可使C2大鼠肝癌细胞系中的GGT活性诱导增加2至3倍。在本研究中，我们分析了在这个定义明确的细胞培养系统中乙醇与类固醇激素及药物之间的相互作用。地塞米松（100 nM），一种合成糖皮质激素激动剂，完全阻止了乙醇对GGT的诱导，但单独添加时没有效果。其他皮质类固醇也观察到了这种抑制作用，但性类固醇没有；糖皮质激素拮抗剂RU 486可阻止这种作用。这些观察结果表明地塞米松通过高亲和力糖皮质激素受体起作用。相反，乙醇在同一细胞中并不干扰糖皮质激素对丙氨酸转氨酶的诱导。我们分析了C2细胞中乙醇的代谢。这些细胞缺乏显著的乙醇脱氢酶活性以及任何细胞色素P-450 Alc免疫反应性。地塞米松并没有改变这些细胞培养基中乙醇的消失情况。我们得出结论，糖皮质激素在细胞水平上与乙醇相互作用，并且这种相互作用不涉及酒精代谢的改变。
