Prenatal alcohol exposure alters the hypothalamic-pituitary-adrenal axis response of immature offspring to interleukin-1: is nitric oxide involved?
We have previously shown that following prenatal alcohol exposure, immature offspring showed blunted ACTH released in response to the peripheral administration of interleukin-1 beta (IL-1 beta). The present studies were conducted to investigate the role of changes in corticosteroid feedback (measured by altered adrenal responses to ACTH), corticotropin-releasing factor (CRF) content of the median eminence (ME), and the influence of endogenous nitric oxide (NO). The injection of several doses of ACTH failed to indicate measurable differences between the corticosterone responses of offspring born to dams fed ad libitum [control (C)], pair-fed (PF), or fed alcohol [ethanol (EtOH) = E]. CRF content in the ME, taken as an index of the amount of releasable peptide, showed a small, but statistically significant, decrease following prenatal alcohol exposure. A comparable change, however, was also noted in PF rats. As expected, the subcutaneous injection of IL-1 beta (0.5 microgram/kg) induced smaller increases in plasma ACTH levels of E than C pups. The response of PF animals was intermediate between that of E and C rats. Finally, we observed that inhibition of NO formation by the administration of the arginine derivative L omega nitro-L-arginine-methylester significantly augmented ACTH secretion in all three experimental groups, and reversed the decreased corticotrophs' response to IL-1 beta caused by prenatal alcohol. Taken together, our results suggest that the ability of prenatal alcohol exposure to alter ACTH released by immature pups in response to blood-borne IL-1 beta is probably not mediated through changes in adrenal responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037.
S
S
Lee
C
C
Rivier
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008473:Median Eminence / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D007375:Interleukin-1; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone