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Am J Physiol Endocrinol Metab 268: E439-E445, 1995;
0193-1849/95 $5.00
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AJP - Endocrinology and Metabolism, Vol 268, Issue 3 E439-E445, Copyright © 1995 by American Physiological Society

ARTICLES

Neonatal phenobarbital-induced defects in age- and sex-specific growth hormone profiles regulating monooxygenases

A. K. Agrawal, N. A. Pampori and B. H. Shapiro
Laboratories of Biochemistry, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6048.

Growth hormone was secreted in sexually dimorphic patterns in both 65- and 150-day-old rats (i.e., "on-off" pulsatile for males and "continuous" pulsatile for females), but as a result of a 200-400% increase in pulse levels the mean concentration of hormone in the circulation was about two times as great in the younger animals. Neonatal exposure to phenobarbital at anticonvulsant therapeutic doses for the rat reduced the pulse amplitudes of circulating growth hormone in both the 65- and 150-day-old males but only in the 65-day-old females. As expected, neonatal administration of the barbiturate produced an almost immediate increase in the activities of the hepatic monooxygenases, as measured by hexobarbital metabolism, which declined to noninduction levels after treatment ceased. Contrary to the well-known transient effects of phenobarbital, at around the time of sexual maturity when gender-dependent differences in hepatic monooxygenases appear (males > females), we observed a second "round" of enzyme induction that persisted in both sexes for the remainder of the study (180 days). Because growth hormone is the primary regulator of sex-dependent hepatic monooxygenases, we have proposed that the abnormal plasma growth hormone profiles produced by neonatal phenobarbital are responsible for the permanent induction of hepatic monooxygenases.


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Middle-Age Alterations in the Sexually Dimorphic Plasma Growth Hormone Profiles: Involvement of Growth Hormone-Releasing Factor and Effects on Cytochrome P450 Expression
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A. K. Agrawal and B. H. Shapiro
Latent Overexpression of Hepatic CYP2C7 in Adult Male and Female Rats Neonatally Exposed to Phenobarbital: A Developmental Profile of Gender-Dependent P450s
J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 1027 - 1033.
[Abstract] [Full Text]


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