Sex- and dose-dependent effects of neonatally administered aspartate on the ultradian patterns of circulating growth hormone regulating hexobarbital metabolism and action.
Rats, neonatally treated with monosodium aspartate (MSA), exhibited developmental defects through adulthood that were characterized by stunted growth, obesity, and reduced size of the liver, kidney, adrenals, and pituitary. Adult male and female rats treated with 4 mg of MSA had no detectable plasma growth hormone as determined from serial blood samples taken every 15 min for 8 consecutive hr. Associated with this loss of circulating growth hormone in the males was a dramatic decline in in vivo and in vitro hexobarbital metabolism and hepatic cytochrome P450 to female levels. The loss of plasma growth hormone in the females had no effect on the already low levels of hepatic monooxygenases. At 2 mg/g body weight, MSA produced both sex- and dose-dependent effects that were far more subtle than the full-blown obesity and growth retardation associated with the larger 4-mg dose. While the mean concentration of circulating growth hormone was reduced 70 to 90% in 2-mg-MSA-treated rats, the sexually dimorphic, ultradian patterns of growth hormone secretion were undisturbed. Affected males continued to secrete a pulse of growth hormone every 3 hr, albeit at greatly reduced amplitudes, interposed by normally undetectable baselines. Similarly, 2-mg-MSA-treated females had greatly reduced mean levels of plasma growth hormone, but with the usual secretion of multiple pulses never dropping to baseline. Surprisingly, the sex-dependent, hepatic monooxygenases, which are normally regulated by the ultradian secretions of growth hormone, were unaffected by the 2-mg MSA treatment. Our results suggest that while an ultradian pulse of circulating growth hormone is necessary for the characteristically male profile of hepatic monooxygenases, neither the amplitude of the secretory peaks nor their total growth hormone content is critical.
Agrawal
A K
AK
Laboratories of Biochemistry, University of Pennsylvania, School of Veterinary Medicine, Philadelphia 19104-6048.
Pampori
N A
NA
Shapiro
B H
BH
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006591:Hexobarbital / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010507:Periodicity; D010902:Pituitary Gland / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013004:Somatostatin / Q000097:blood*
D001224:Aspartic Acid; D013004:Somatostatin; D006591:Hexobarbital