Shapiro B H, Pampori N A, Ram P A, Waxman D J
Laboratory of Biochemistry, University of Pennsylvania, School of Veterinary Medicine, Philadelphia.
J Pharmacol Exp Ther. 1993 May;265(2):979-84.
Neonatal exposure to monosodium glutamate (MSG) permanently blocks growth hormone (GH) secretion, which results in the development of a well-defined syndrome characterized by stunted body growth, obesity and impaired drug metabolism. We have found that restoration of the normal masculine circulating profile of GH (i.e., six daily pulses) by use of an external pumping apparatus is ineffective in restoring the normal expression of hepatic cytochrome P450 2C11, a major GH-dependent drug and steroid metabolizing enzyme that is eliminated by MSG treatment. Moreover, administering GH at two, four or seven plasma pulses per day with amplitudes ranging from physiologic to 7 times normal were similarly ineffective in restoring the expression (at both an activity and mRNA level) of the cytochrome. Additionally, multicytochrome P450-dependent hexobarbital hydroxylase was also unresponsive to GH administration in the MSG-treated rats. Because GH replacement was unable to correct the enzyme defects, our results suggest that the developmental abnormalities produced by neonatal MSG are not simply a result of a GH deficiency per se, but are due to an irreversible insensitivity of the target cell to GH.
新生儿期接触味精（MSG）会永久性地阻断生长激素（GH）的分泌，这会导致一种明确的综合征的出现，其特征为身体生长发育迟缓、肥胖以及药物代谢受损。我们发现，通过使用外部泵装置恢复GH正常的男性循环模式（即每日六次脉冲），对于恢复肝脏细胞色素P450 2C11的正常表达无效，细胞色素P450 2C11是一种主要的依赖GH的药物和类固醇代谢酶，在MSG处理后会被消除。此外，每天以两个、四个或七个血浆脉冲的频率给予GH，幅度从生理水平到正常水平的7倍，同样无法恢复细胞色素的表达（在活性和mRNA水平上）。另外，在MSG处理的大鼠中，多细胞色素P450依赖性的己巴比妥羟化酶对GH给药也没有反应。由于GH替代无法纠正酶缺陷，我们的结果表明，新生儿期MSG产生的发育异常并非仅仅是GH缺乏本身的结果，而是由于靶细胞对GH产生了不可逆的不敏感性。
