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: 3320232
• 负责人: Michael Selmanoff
• 金额: $ 12.56万
• 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/3320232
• 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.

该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。拟议的研究检查了下丘脑机制 高催乳素血症 (HP) 和睾酮 (T) 可能会抑制强直性 LE 分泌 在雄性大鼠中。这个问题对于控制 哺乳动物的生育力和避孕具有深远的意义。 我们将利用急性、可逆的高催乳素血症模型 是与剂量相关的、对去势后 LH 升高的暂时抑制 绵羊 PRL (oPRL) 给药产生的水平。这个动物模型 使我们能够研究对大脑和垂体的直接影响 在没有混杂因素的情况下，高催乳素血症对强直性 LH 释放的影响 性腺的影响。 我们将分析所选择的、增加的给药剂量的效果 oPRL 对脉动 LH 分泌的频率和幅度的影响。 去甲肾上腺素 (NE)、肾上腺素、多巴胺和 GABA 的合成和周转 速率常数将按完整、阉割、 经去势PRL治疗和去势T治疗的大鼠，在显微解剖的大脑中 LH-RH 上这些神经元可能的突触位点的区域 神经元。将利用定量原位杂交组织化学 确定 PRL 和 T 是否影响单细胞谷氨酸水平 内侧视前区 (MPoA) GABA 能神经元中的脱羧酶 mRNA。 HP 是否会抑制由新方法估计的中位隆起 LH-RH 周转率 秋水仙碱方法，或阻断 LH 对第三心室 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。在这个 可逆模型，大脑参数将在之前（哦），'期间确定 (48小时)和后(96小时)PRL抑制去势后LH上升，因此 评估哪些终点在最大抑制时（48小时）发生变化，以及 这些变化是否逆转或其他变化是否出现在逆转时间（96小时）。 这项研究将进一步加深我们对下丘脑机制的理解 调节 LH 和 PRL 分泌以及升高循环的方式 PRL 水平和反馈类固醇影响这些机制。