NEUROENDOCRINOLOGICAL ROLES OF HISTAMINE IN THE HYPOTHALAMO-HYPOPHYSEAL SYSTEM

根据本实验室阐明的组胺能神经系统在大鼠脑内的分布，认为组胺在下丘脑-垂体神经内分泌系统中起着重要的神经调节剂作用。为了解其在神经内分泌调节中的作用，我们研究了生理刺激下丘脑分泌垂体激素后下丘脑组胺浓度的变化，以及用组氨酸脱羧酶的特异性抑制剂α-氟甲基组氨酸(FMH)耗竭神经元组胺对血浆激素水平的影响。研究结果如下：1.研究结果。在含有组胺能神经元胞体的下丘脑后部，我们发现组胺含量有明显的昼夜节律。在慢性I.C.V.之后。给予FMH后，血浆皮质酮水平的日变化明显减弱。双侧肾上腺切除后，下丘脑后部组胺含量降低，下丘脑前部组胺含量升高。在慢性IP之后。给予FMH可完全抑制双侧肾上腺切除后血浆ACTH的显著升高。给予高渗盐水后，血浆加压素水平和下丘脑组胺含量均升高。慢性给药FMH i.c.v.此外，利用体外序贯灌流系统，我们发现&lt；H_1&Gt；-受体参与了促黄体生成素的分泌。此外，我们用一种更灵敏的检测组胺能终末的方法研究了组胺能终末在大鼠脑内的详细分布，发现下丘脑核团，如室旁核、视上核、正中隆起和神经垂体中有致密的纤维网络。这些神经化学和组织化学结果支持我们的假设，即组胺是神经内分泌系统中的神经调节剂。

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.