NEUROENDOCRINE REGULATION OF LH AND PROLACTIN SECRETION

LH 和催乳素分泌的神经内分泌调节

• 批准号: 3320233
• 负责人: Michael Selmanoff
• 金额: $ 12.83万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3320233
• 关键词: brain mapping; disease /disorder model; dissection; dopamine; epinephrine; gamma aminobutyrate; glutamate decarboxylase; high performance liquid chromatography; hormone inhibitor; hormone regulation /control mechanism; hyperprolactinemia; hypothalamus; in situ hybridization; laboratory rat; luteinizing hormone; male castration; median eminence; neural information processing; neuroendocrine system; neuronal transport; neurons; neurotransmitter metabolism; norepinephrine; pituitary gland; preoptic areas; prolactin; prolactin releasing /inhibiting factor; radioimmunoassay; testosterone

The longterm objective of this research program is to determine the neuroendocrine mechanisms regulating LH and prolactin (PRL) secretion in mammals. Proposed studies examine hypothalamic mechanisms by which hyperprolactinemia (HP) and testosterone (T) may inhibit tonic LE secretion in male rats. This problem is of central importance in the control of mammalian fertility and has profound contraceptive significance. We will utilize an acute, reversible hyperprolactinemia model where there is a dose-related, transitory suppression of the postcastration rise in LH levels produced by ovine PRL (oPRL) administration. This animal model allows us to investigate the direct brain and pituitary effects of hyperprolactinemia on tonic LH release in the absence of confounding gonadal influences. We will analyze the effects of selected, increasing doses of administered oPRL on the frequency and amplitude of pulsatile LH secretion. Norepinephrine (NE), epinephrine, dopamine and GABA synthesis and turnover rate constants will be determined in intact, castrated, castrated-PRL-treated and castrated-T-treated rats, in microdissected brain regions which are likely sites of synapse of these neurons on LH-RH neurons. Quantitative in situ hybridization histochemistry will be utilized to determine whether PRL and T affect single cell levels of glutamic acid decarboxylase mRNA in medial preoptic area (MPoA) GABAergic neurons. Whether HP inhibits median eminence LH-RH turnover estimated by a new colchicine method, or blocks the LH response to third ventricular NE, MPOA infused bicuculline or iv N-methyl-D-aspartate will be ascertained. In this reversible model, brain parameters will be determined before (Oh),' during (48h) and after (96h) PRL suppression of the postcastration LH rise, thus assessing which endpoints change at a time of maximal suppression (48h) and whether these changes reverse or others appear at a time of reversal (96h). This research will further our understanding of the hypothalamic mechanisms regulating LH and PRL secretion and the ways in which elevated circulating PRL levels and feedback steroid affect these mechanisms.

本研究计划的长期目标是确定 调节LH和催乳素（PRL）分泌的神经内分泌机制 哺乳动物拟议的研究检查下丘脑机制， 高催乳素血症（HP）和睾酮（T）可抑制LE的紧张性分泌 在雄性大鼠中。这个问题在控制 哺乳动物的生育能力，并具有深刻的避孕意义。 我们将利用急性、可逆性高催乳素血症模型， 是对去势后LH升高的剂量相关的短暂抑制 通过绵羊PRL（oPRL）给药产生的水平。该动物模型 使我们能够研究直接的大脑和垂体的影响， 在无混杂因素的情况下，高泌乳素血症对紧张性LH释放的影响 性腺的影响 我们将分析选定的，增加剂量的管理的影响， oPRL对LH脉冲分泌频率和幅度的影响。 去甲肾上腺素（NE）、肾上腺素、多巴胺和GABA的合成和周转 将在完整的，去势的， 去势PRL处理和去势T处理大鼠，在显微解剖的脑中 LH-RH上可能是这些神经元突触的区域 神经元将使用定量原位杂交组织化学 以确定PRL和T是否影响谷氨酸的单细胞水平 内侧视前区（MPoA）GABA能神经元脱羧酶mRNA。 HP是否抑制中位隆起LH-RH周转， 秋水仙碱法，或阻断LH对第三脑室NE，MPOA的反应 将确定输注荷包牡丹碱或静脉注射N-甲基-D-天冬氨酸。在这 在可逆模型中，大脑参数将在（Oh）之前确定， (48h)在去势后（96小时）PRL抑制LH升高，因此 评估哪些终点在最大抑制时间（48小时）发生变化， 这些变化是否逆转或在逆转时（96小时）出现其他变化。 这一研究将进一步加深我们对下丘脑机制的理解 调节LH和PRL的分泌，以及提高循环 PRL水平和反馈类固醇影响这些机制。