INVOLVEMENT OF HISTAMINE IN SUCKLING-INDUCED RELEASE OF OXYTOCIN, PROLACTIN AND ADRENOCORTICOTROPIN IN LACTATING RATS

We have previously shown that histaminergic neurons participate in med iation of the prolactin (PRL), adrenocorticotropin (ACTH) and oxytocin responses to physiological stimuli such as stress and dehydration. Si nce suckling is a potent stimulus for the secretion of these three hor mones, we investigated the mediating role of neuronal histamine in suc kling-induced release of oxytocin, PRL and ACTH in conscious lactating rats. The animals were pretreated with the histamine synthesis inhibi tor alpha-fluoromethylhistidine, the H-1 receptor antagonist mepyramin e, the H-2 receptor antagonist cimetidine or the H-3 receptor agonist R(alpha)methylhistamine, which by binding to H-3 autoreceptors inhibit s histamine release and synthesis. After the lactating rats were separ ated from their pups for 240 min, the pups were returned for a sucklin g period of 20 min. Thereafter the mothers were sacrificed by decapita tion and trunk blood was collected for determination of hormones. Lact ating rats not exposed to suckling served as controls. Suckling increa sed oxytocin 2-fold, PRL 50-fold and ACTH 5-fold. Blockade of histamin e synthesis by alpha-fluoromethylhistidine or histamine release by R(a lpha)methylhistamine reduced the suckling-induced secretion of the thr ee hormones significantly. Blockade of postsynaptic H-1 receptors by m epyramine inhibited the hormone responses to suckling, while the block ade of postsynaptic H-2 receptors by cimetidine decreased the suckling -induced oxytocin and PRL release but did not affect the ACTH release. None of the compounds affected oxytocin, PRL or ACTH secretion in lac tating mothers not exposed to suckling. In addition, suckling signific antly increased the mRNA of the histamine synthesizing enzyme histidin e decarboxylase in the ventrolateral tuberomammillary nucleus by 1.5-f old, indicating that the stimulus of suckling enhances the neuronal hi stamine synthesis. We conclude that suckling increases neuronal histam ine synthesis and that histaminergic neurons by activation of postsyna ptic H-1 and H-2 receptors are involved in the hypothalamic mediation of oxytocin, PRL and ACTH responses to suckling. These findings furthe r substantiate a role of neuronal histamine in the neuroendocrine regu lation of pituitary hormones in response to physiological stimuli.