Badger T M, Ronis M J, Lumpkin C K, Valentine C R, Shahare M, Irby D, Huang J, Mercado C, Thomas P, Ingelman-Sundberg M
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
J Pharmacol Exp Ther. 1993 Jan;264(1):438-47.
Growth hormone (GH) secretion is sexually dimorphic in the laboratory rat and the plasma GH profile is a determining factor in the regulation of the male-specific cytochrome P450 (CYP) 2C11. Acute ethanol has been reported previously to alter the secretion of GH, and in the present investigation, we have studied the effects of chronic (38 days) ethanol on plasma GH profiles, CYP 2C11 and the major ethanol-inducible cytochrome, CYP 2E1, using a total enteral nutrition system, where 35% of the total calories were ethanol. Ethanol-treated rats had elevated (P < or = .05) CYP 2E1 activities and apoprotein levels and increased steady-state mRNA levels encoding for CYP 2E1. Ethanol-treated rats also had reduced (P < or = .05) hydroxylation of testosterone at positions 2 alpha and 16 alpha, lower 2C11 apoprotein levels and lower steady-state mRNA levels encoding for 2C11. In addition, the plasma GH pulse profiles were altered in chronically treated rats by reducing (P < or = .05) the GH pulse amplitude and mean plasma GH concentrations. Our results suggest that: 1) the reduced CYP 2C11 activities, apoprotein levels and steady-state mRNA levels during chronic alcohol exposure are causally related to the alterations in GH secretion; and 2) chronic alcohol exposure elevated CYP 2E1 activities, apoprotein levels and steady-state mRNA levels, and these changes occurred primarily as the result of ethanol rather than undernutrition or as the combination of ethanol and undernutrition.
生长激素（GH）的分泌在实验大鼠中存在性别差异，血浆GH水平是雄性特异性细胞色素P450（CYP）2C11调节的决定因素。先前有报道称急性乙醇会改变GH的分泌，在本研究中，我们使用全肠内营养系统，其中总热量的35%为乙醇，研究了慢性（38天）乙醇对血浆GH水平、CYP 2C11以及主要的乙醇诱导细胞色素CYP 2E1的影响。乙醇处理的大鼠CYP 2E1活性和载脂蛋白水平升高（P≤0.05），编码CYP 2E1的稳态mRNA水平增加。乙醇处理的大鼠在2α和16α位睾酮的羟化作用也降低（P≤0.05），2C11载脂蛋白水平降低，编码2C11的稳态mRNA水平降低。此外，长期处理的大鼠血浆GH脉冲水平发生改变，GH脉冲幅度和平均血浆GH浓度降低（P≤0.05）。我们的结果表明：1）慢性酒精暴露期间CYP 2C11活性、载脂蛋白水平和稳态mRNA水平降低与GH分泌改变存在因果关系；2）慢性酒精暴露使CYP 2E1活性、载脂蛋白水平和稳态mRNA水平升高，这些变化主要是乙醇的结果，而非营养不良或乙醇与营养不良共同作用的结果。
