Hypophysiotropic role and hypothalamic gene expression of corticotropin-releasing factor and vasopressin in rats injected with interleukin-1 beta systemically or into the brain ventricles.
Intact adult male rats were injected intravenously (i.v., 400 ng/kg), intraperitoneally (i.p., 400 ng/kg) or intracerebroventricularly (i.c.v., 100 ng/kg) with interleukin-1 beta (IL-1 beta) or its vehicle. In comparison with vehicle-treated animals, IL-1 beta induced significant (P < 0.01) increases in plasma ACTH levels measured 30 min later regardless of the route of cytokine administration. These changes were markedly blunted in rats administered specific antibodies directed against corticotropin-releasing factor (CRF). In contrast, vasopressin (VP) antibodies significantly blunted ACTH released by the i.c.v. injection of IL-1 beta, but only modestly altered the effect of the systemic injection of the cytokine. We then used semi-quantitative in situ hybridization analysis to measure changes in steady-state mRNA levels, as they might occur in response to these same doses of IL-1 beta. Following administration of the vehicle, measurement of gene expression in the paraventricular (PVN) portion of the hypothalamus indicated a measurable amount of hybridization signals for both CRF and VP. No detectable changes in either CRF or VP gene expression were observed in rats injected with IL-1 beta i.v. or i.p. 5 h earlier. In contrast, the i.c.v. administration of the cytokine significantly (P < 0.01) increased both CRF and VP mRNA levels measured 5 h later. These results suggest that while endogenous CRF modulates the response of the corticotrophs to this cytokine regardless of the route of administration, the role of VP is more important in rats injected centrally than in those injected peripherally.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
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Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037.
Rivier
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C
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism*; D017403:In Situ Hybridization; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000502:physiology*; D015347:RNA Probes; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D007375:Interleukin-1; D015347:RNA Probes; D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone