CONCOMITANT ASSOCIATION BETWEEN HIGH PLASMA LEVELS OF GROWTH HORMONE AND LOW HEPATIC MIXED-FUNCTION OXIDASE ACTIVITY IN THE YOUNG RAT

¹ Division of Pediatric Clinical Pharmacology, Departments of Pediatrics and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee and Department of Medicine, State University of New York at Buffalo, Buffalo, New York

The present study was designed to test the hypothesis that growth hormone is a modulator of liver drug metabolic enzyme activity in the young rat. Radioimmunoassayable rat growth hormone (RGH) and components and activity of the liver mixed-function oxidase system were measured in animals —3 to 324 days of age. The mean level of plasma RGH in animals —3 to 10 days of age was higher than the mean of all rats 21 to 324 days of age. A nadir in the level of RGH was noted in rats 21 to 25 days old with an increase to approximate fluctuating adult levels observed in 40-to 50-day-old animals. The hepatic metabolism of hexobarbital, aminopyrine and ethylmorphine was low in fetal and pre-weanling animals whereas the hydroxylation of aniline approached adult levels by 10 days of age. The specific postnatal pattern of maturation for this mixedfunction oxidase system depended on the drug-substrate used. The extent and rate of reduction of cytochrome P-450 were low in the fetus and newborn with an increase toward adult levels noted at about 21 days. The developmental profile of electron transport components was dependent on the cytochrome (P-450 or c) used as the acceptor of reducing equivalents and, for cytochrome P-450 reductase, whether the reaction was measured in the presence or absence of hexobarbital. The liver metabolism of hexobarbital and aniline, content of cytochrome P-450 and rate of cytochrome c reduction showed an inverse correlation with the plasma level of RGH in rats —3 to 25 days of age. Growth hormone may modulate development of the liver mixed-function oxidase system in the rat by decreasing flow of reducing equivalents at the level of cytochrome P-450.