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Mode of steroid action involving in the behavioral regulation

涉及行为调节的类固醇作用方式

基本信息

批准号：
05640749
负责人：
TSUTSUI Kazuyoshi
金额：
$ 1.34万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Avian reproductive behaviors are under androgen regulation.To identify the neuropetides that are implicated in the regulation of steroid hormone dependent behavioral processes in birds.We have isolated three opioid peptides, i.e.Met-and Leu-enkephalins and Met-enkephalin-Arg-Phe.This is the first direct demonstration of the presence of opioid peptides in the avian brain.All of the three opioid peptides inhibited the spontaneous firing activities of subsets of neurons in the preoptic and hypothalamic areas that are known to be involved in the regulation of several reproductive behavior.Such an effect was completely blocked by naloxone, an opioid receptor antagonist.It may be possible that opioid peptides regulate some reproductive behavior through the mechanism that provokes the inhibition of neuronal activities.It is well known that the brain is a target site of steroid hormones supplied by peripheral steroidogenic glands.However, present biochemical experiments demonstrated that the avian brain produces pregnenolone from cholesterol.Most accumulation of pregnenolone in the brain may be independent of the peripheral endocrine gland system.To understand the localization of cells involving with pregnenolone synthesis, the immunohistochemical study with the antibody against cytochrome P450_<scc> was further undertaken in the avian brain.Clusters of immunoreactive cell bodies were detected in several telencephalic, diencephalic and mesencephalic regions.An intense immunoreaction was detected in somata of Purkinje cells and in the dendrites extending through the cerebellar molecular layr.Western immunoblot analysis with the P450scc antibody confirmed the presence of a P450scc-like substance in these brain regions.Immunohistochemistry using a specific marker protein of glial cells revealed that both neuronal and glial cells possess a P450scc-like substance in the avian brain.

鸟类的生殖行为受雄激素的调控。识别与鸟类类固醇激素依赖行为过程的调节有关的神经肽。我们分离了三种阿片肽，即met -和leu -脑啡肽和met -脑啡肽- arg - phe。这是第一次直接证明阿片肽存在于鸟类大脑中。所有这三种阿片肽都抑制了视前区和下丘脑区神经元亚群的自发放电活动，这些神经元亚群参与了几种生殖行为的调节。这种作用被阿片受体拮抗剂纳洛酮完全阻断。阿片肽可能通过抑制神经元活动的机制来调节某些生殖行为。众所周知，大脑是外周类固醇生成腺提供类固醇激素的靶部位。然而，目前的生物化学实验表明，鸟类大脑从胆固醇中产生孕烯醇酮。大多数孕烯醇酮在脑内的积累可能与外周内分泌腺系统无关。为了了解孕烯醇酮合成相关细胞的定位，我们进一步在禽脑中进行了抗细胞色素P450_<scc>抗体的免疫组织化学研究。在几个端脑、间脑和中脑区检测到免疫反应性细胞体簇。浦肯野细胞体和贯穿小脑分子层的树突均有强烈的免疫反应。P450scc抗体的Western免疫印迹分析证实在这些脑区存在P450scc样物质。利用神经胶质细胞特异性标记蛋白的免疫组化发现，鸟类脑内的神经元细胞和神经胶质细胞都具有p450scc样物质。