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NEUROENDOCRINOLOGICAL ROLES OF HISTAMINE IN THE HYPOTHALAMO-HYPOPHYSEAL SYSTEM

组胺在下丘脑-垂体系统中的神经内分泌作用

基本信息

批准号：
60480135
负责人：
YAMATODANI Atsushi
金额：
$ 3.97万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

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.

从本实验室已阐明的大鼠脑内组胺能神经元系统的分布，我们认为组胺在下丘脑-垂体神经内分泌系统中起着重要的神经调质作用。为了解组胺在神经内分泌调节中的作用，我们研究了生理刺激垂体激素分泌后下丘脑中组胺浓度的变化，以及用组氨酸脱羧酶特异性抑制剂α-氟甲基组氨酸（FMH）去除神经元组胺对血浆激素水平的影响。研究结果如下：1.在下丘脑后部含有组胺能神经元胞体的区域，我们发现组胺含量有明显的昼夜节律。长期静脉注射FMH后，血浆皮质酮水平的明显昼夜变化减小.双侧肾上腺切除后，下丘脑后部组胺含量减少，前部组胺含量增加。长期腹腔注射FMH后，双侧肾上腺切除引起的血浆ACTH的显著升高被完全抑制.高渗盐水给药引起血浆加压素水平和下丘脑组胺含量增加。长期静脉注射FMH可抑制注射生理盐水引起的血浆加压素水平的升高。此外，我们还利用体外序贯灌流系统，发现<H_1>β受体参与了LH-RH的分泌。此外，我们还用一种更灵敏的方法观察了组胺能神经末梢在大鼠脑内的分布，发现在下丘脑室旁核、视上核、正中隆起和神经垂体等核团内有密集的纤维网络，这些结果支持了我们的假设，即组胺是神经内分泌系统中的一种神经调质。