Over-expression of CYP2C11, the major male-specific form of hepatic cytochrome P450, in the presence of nominal pulses of circulating growth hormone in adult male rats neonatally exposed to low levels of monosodium glutamate.
Male rat pups were injected with monosodium glutamate (MSG), 4 mg/g b.wt., on either days 1 and 3 or days 1, 3, 5, 7 and 9 of life. Plasma samples obtained during 8.5 continuous hr of serial blood collections from adults, neonatally treated with five doses of MSG, contained no detectable concentrations of growth hormone. In addition, the livers of these animals contained no measurable expression levels of the major male-specific form of cytochrome P450 (CYP2C11) mRNA or its protein. In contrast, adult male rats treated with only two neonatal injections of MSG exhibited typical masculine profiles of growth hormone release, except that the amplitudes of the ultradian pulses were reduced to about 10 to 20% of normal male levels. Otherwise, like control males the peaks occurred about every 3.5 to 4 hr and the intervening 3-hr troughs had undetectable concentrations of growth hormone. Moreover, the livers of these twice-injected MSG-treated rats over-expressed CYP2C11 as indicated by a 200% increase in CYP2C11 mRNA and a concomitant 30 to 40% increase in CYP2C11 protein and its catalytic activities. The effectiveness of minipulses of growth hormone, mimicking the pattern found in MSG-treated animals, to induce over-expression of hepatic CYP2C11 in hypophysectomized rats, suggests that the supraexpression of CYP2C11 found in the MSG-treated animals may be explained, in part, by the abnormal profiles of circulating growth hormone induced by neonatal exposure to the amino acid. In conclusion, depending upon neonatal exposure levels, MSG can produce permanent, yet very different defects in the adult male patterns of growth hormone secretion and growth hormone-dependent CYP2C11 expression.
Laboratory of Biochemistry, University of Pennsylvania, School of Veterinary Medicine, Philadelphia.
N A
NA
Pampori
B H
BH
Shapiro
D000818:Animals; D000831:Animals, Newborn; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D012970:Sodium Glutamate / Q000633:toxicity*; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; C021352:hexobarbital hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; D012970:Sodium Glutamate