NEUROENDOCRINOLOGICAL ROLES OF HISTAMINE IN THE HYPOTHALAMO-HYPOPHYSEAL SYSTEM

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From the distribution of the histaminergic neuron system in rat brain, elucidated in our laboratory, it is considered that histamine plays some important roles as a neuromodulator in the hypothalamo-hypophyseal neuroendocrine system. To know its roles in the neuroendocrine regulation, we studied changes in histamine concentration in the hypothalamus after physiologically stimulating hypophyseal hormone secretion and effects of depletion of neuronal histamine using alfa-fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase, on the hormone level in plasma. The results are as follows.1. In the posterior hypothalamic area which contains cell bodies of the histaminergic neurons, we found a clear circadian rhythm in histamine contents. After chronic i.c.v. administration of FMH, the clear diurnal variation of the plasma corticosterone levels was diminished.2. Bilateral adrenalectomy caused decrease of histamine contents in the posterior hypothalamus and increase of those in the anterior hypothalamus. After chronic i.p. administration of FMH, the marked increase of plasma ACTH by bilateral adrenalectomy was completely suppressed.3. Administration of hyperosmotic saline caused increase of both plasma vasopressin levels and hypothalamic histamine contents. Chronic administration of FMH i.c.v. suppressed the increase of plasma vasopressin induced by the saline injection.In addition, using in vitro sequential perifusion system, we found involvement of <H_1> -receptor in LH-RH secretion. Furthermore, we examined the detailed distribution of histaminergic terminals in the rat brain using a more sensitive method for detecting histaminergic terminals, and found that dense networks of the fibers in the hypothalamic nuclei, such as the paraventricular and supraoptic nucleus, the median eminence, and neurohypophysis.These neurochemical and histochemical findings support our hypothesis, that is, histamine is a neuromodulator in the neuroendocrine system.