Altered ACTH and corticosterone responses to interleukin-1 beta in male rats exposed to an alcohol diet: possible role of vasopressin and testosterone.
We have previously shown that female rats exposed to an alcohol (ethanol, E) diet exhibited a blunted ACTH response to systemically administered interleukin-1 beta (IL-1 beta). Because of the presence of gender differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and of the possible role played by sex steroids in modulating the inhibitory influence of E in females, we studied the ability of a 10-day E diet to alter ACTH and corticosterone secretion of intact or castrated male rats injected with IL-1 beta or endotoxin, a releaser of endogenous cytokines. Pituitary responsiveness to secretagogues that mediate the endocrine effects of IL-1 beta, namely corticotropin-releasing factor (CRF) and vasopressin (VP), was also investigated. The ACTH responses of animals fed ad libitum (C group) or pair-fed (PF group) to the intravenous administration of IL-1 beta or endotoxin were not statistically different (p > 0.05); therefore, results from these two groups were combined in the initial experiments. Subsequent experiments only used E and C animals. When compared with this latter group, intact E males showed a significant (p < 0.01) decrease in ACTH levels measured 30 and 60 min after the intravenous injection of IL-1 beta or endotoxin. In contrast, E rats released as much corticosterone as C rats in response to IL-1 beta, but significantly (p < 0.05) more following administration of endotoxin (lipopolysaccharide). The stimulatory effect of VP on ACTH release was also measurably blunted by alcohol, whereas that of CRF was not. In none of these experiments were any significant differences observed between C and PF rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
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S
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037, USA.
Rivier
C
C
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000502:physiology*; D014667:Vasopressins / Q000502:physiology*
D007375:Interleukin-1; D014667:Vasopressins; D013739:Testosterone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone