Rat hypothalamic corticotropin-releasing hormone secretion [formula omitted] is stimulated by interleukin-1 in an eicosanoid-dependent manner

Abstract

We studied the effect of interleukin-1α (IL-1) on corticotropin-releasing hormone (CHR) secretion by explanted rat hypothalami in vitro . We also assessed possible mediation of arachidonic acid metabolites on IL-1-stimulated CRH secretion, by preincubating hypothalami with the cyclooxygenase inhibitor indomethacin (INDO, 1 μM), the lipooxygenase and ciclooxygenase inhibitor eicosatetraynoic acid (ETYA, 10 μM), or the lipooxygenase inhibitor nordihydroguaiaretic acid (NDGA, up to 30 μM). In additional experiments, prostaglandins (PG) Ez and Fzα were added to the cultures treated with INDO or ETYA. Finally, we investigated the effect of dexamethasone (DEX) on IL-1-stimulated CRH secretion. IL-1 stimulated immunoreactive CRH (iCRH) secretion by explanted hypothalami in a concentration-dependent fashion. Both INDO and ETYA inhibited IL-1-(10nM)-stimulated iCRH secretion, whereas NDGA did not have any effect. The addition of PGFzα (10 nM) restored the secretion of iCRH inhibited by INDO. DEX treatment significantly inhibited IL-1-stimulated iCRH release. Our results suggest that the stimulatory effect of IL-1 on the hypothalamic CRH neuron is mediated by the cyclooxygenase metabolites of arachidonic acid, and, among others, by PGFzα.