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Growth Hormone Modulation of Liver Drug Metabolic Enzyme Activity in the Rat II. Specificity of the Hormone Effect 1

Summary The specificity of growth hormone (GH) on liver drug metabolic enzyme activity was examined by (a) injecting rats with one of three hormones [GH, prolactin, or human chorionic somatomammotropin (HCS)] known to have similar structural and biological characteristics, and (b) by treating animals with nonhormonal polypeptides (albumin or globulin) or an amino acid mixture similar in composition to the amino acid content of human GH. The liver metabolism of hexobarbital, ethylmorphine, aniline and p-nitrobenzoic acid (PNBA) and the rate and extent of cytochrome P-450 reduction showed a dose-dependent decrease following injection of GH. Boiling the GH reduced its effectiveness. With the exception of ethylmorphine and PNBA metabolism, prolactin did not decrease activity of this metabolic system. When one dose of HCS was studied, the metabolism of hexobarbital was slightly decreased and that of aminopyrine was slightly increased. The spectrum of effects of GH on the overall rate of drug metabolism and on components of the microsomal cytochrome P-450 system could not be reproduced with the nonhormonal polypeptides or with the amino acid mixture. It is concluded that, within the dose and time periods used for this study, the decreased steady state level of liver drug metabolism is a relatively specific action of GH in the rat. The technical assistance of Dr. J. Chrastil, Messrs. B. Briscoe, K. Dill, G. Colin, Mrs. S. Skrivseth, the secretarial assistance of Mrs. K. Miller, Mrs. S. Burke, and the helpful advice of Dr. Ian Burr are gratefully acknowledged.