THE ADRENOCORTICOTROPIN RESPONSE TO INTERLEUKIN-1-BETA INSTILLED INTO THE RAT MEDIAN-EMINENCE DEPENDS ON THE LOCAL RELEASE OF CATECHOLAMINES

Interleukin-1β (IL-1β) is a potent ACTH secretagogue which activates the release of hypothalamic CRF but is unable to cross the blood brain barrier. Recently, it was reported that IL-1β, instilled directly into the hypothalamic median eminence (ME), rapidly induced ACTH secretion. Thus, due to the lack of a blood brain barrier the ME appears to be a site whereby iv IL-1β can access the brain to stimulate CRF and, consequently, ACTH secretion. To evaluate the role of central catecholamines in this process, 250 g male rats were lesioned with 6-hydroxy-dopamine instilled into the lateral ventricle. Ten days later, rats received recombinant h-IL-1β (10 or 30 ng) into the ME and blood was sampled via indwelling jugular cannulae. The ACTH response to IL-1β, 30 ng, was reduced by approximately 50% in the lesioned rats (P = 0.05), and it was abolished in those receiving IL-1β, 10 ng (P < 0.05). Moreover, in rats given iv IL-1β (1 µg), 6-hydroxy-dopamine significantly reduced the ACTH response by more than 50% (P < 0.001). To determine the effect of acute epinephrine depletion, 2, 3 dichloro-a-methylbenzylamine (DCMB, 60 mg/kg BW) and SKF64139 (SKF) (100 mg/kg BW), inhibitors of the enzyme which converts norepinephrine to epinephrine, were administered ip 4 h before intra-ME IL-1β (30 ng). DCMB reduced the ACTH response by 80% and SKF reduced it to its own baseline. LY 10853, which acutely depletes both norepinephrine and epinephrine, also reduced the ACTH response by 80%. Because of the reported capacities of DCMB and SKF to block α2adrenoreceptors in vitro, yohimbine, an α2receptor antagonist, was studied. Intra- ME yohimbine failed to inhibit the ACTH response to intra- ME IL-10. In contrast, a significant (P < 0.01) dose-dependent, reduction in the ACTH response to intra-ME IL-1β (30 ng) was observed in rats pretreated with either a nonselective a or β adrenoreceptor antagonist (phentolamine, 2-40 ng or propranolol, 2-20 ng, respectively, into the ME). In contrast, intra-ME phentolamine, 20 ng, failed to reduce the ACTH response to iv CRF, 1 Mg/kg BW. Thus, the secretion of ACTH stimulated by the action of IL-1β at the ME depends, in part, on the local secretion of norepinephrine and epinephrine interacting with both a and β adrenergic receptors. © 1990 by The Endocrine Society.