Neonatal phenobarbital-induced defects in age- and sex-specific growth hormone profiles regulating monooxygenases.
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.
Agrawal
A K
AK
Laboratories of Biochemistry, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6048.
Pampori
N A
NA
Shapiro
B H
BH
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D006591:Hexobarbital / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010507:Periodicity; D010634:Phenobarbital / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D013006:Growth Hormone; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; C021352:hexobarbital hydroxylase; D010634:Phenobarbital