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CENTRAL NERVOUS SYSTEM REGULATION OF REPRODUCTION

中枢神经系统对生殖的调节

基本信息

批准号：
3310154
负责人：
CHARLES A BARRACLOUGH
金额：
$ 22.18万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-09-01 至 1994-05-31
项目状态：
已结题

项目摘要

The general purpose of this proposal is to analyze some of the complex interactions which exist between neurotransmitter and peptidergic neurons within the hypothalamus. To learn more of how axons from the locus coeruleus (LC) and the medullary Al and A2 regions projects to hypothalamic regions containing LHRH neurons, specific transections and lesions within the hypothalamus will be made. Recent studies show that all LC stimulatory NE axons decussate to reach contralateral LHRH neurons. In these and other studies, anesthetized, estrogen-treated ovariectomized rats will have their medial preoptic nucleus (MPN) electrochemically stimulated (ECS) and, thereafter, the LC, A1 or A2 cell groups will be electrically stimulated (ES). Such LC or A1 ES amplifies LH release. Other studies will examine whether neuroexcitant drugs (e.g. 3-isobutyl-methylxanthine) active NE secretion when microinfused into LC or A1 of unanesthetized rats. The paragigantocellularis nucleus (PGC) in the ventrolateral medulla regulates LC neuronal activity, presumably by releasing excitatory amino acids (EAA). ES of PGC on will be performed to determine if such stimuli increase hypothalamic NE secretion. Other studies will evaluate whether the microinfusion of EAA into LC has a similar excitatory effect in releasing NE and LHRH/LH. Since LHRH neurons may be activated only when specifically coded noradrenergic signals are presented, the parameters of LC or A1 ES will be varied to study how such stimuli affect LHRH neuronal activity. As NE may act via a GABA interneuron, the role of hypothalamic GABA neurons in the regulation of NE-induced LHRH release will be examined. The role of the opiate system in modulating NE secretion also will be studied. In these experiments, specific agonists or antagonists of GABA or opiate receptors will be placed into selective hypothalamic, mid or hindbrain regions and their effects on NE and LHRH secretion following mid or hindbrain ES will be assessed. Changed in NE and LHRH secretion after LC, A1 and A2 ES will be evaluated by HPLC and RIA in dialysates obtained from microdialysis probes placed into specific hypothalamic areas and the pituitary gland. The serotonin (5-HT) system also is to be studied with particular emphasis on how 5-HT and NE interact to excite or inhibit LHRH neuronal activity. Finally, NE and 5-HT interactions with LHRH neurons in androgen-sterilized and male rats are to be examined. These studies should provide important fundamental new information on how the neuroendocrine brain functions to evoke preovulatory gonadotropin surges and ovulation.

本提案的总体目的是分析一些神经递质和神经元之间存在着复杂的相互作用，下丘脑内的肽能神经元。了解更多关于来自蓝斑（LC）和延髓A1和A2的轴突区域投射到含有LHRH神经元的下丘脑区域，下丘脑内的特定横断和病变将被进行了最近的研究表明，所有LC刺激NE轴突交叉到达对侧LHRH神经元。在这些及其它研究中，麻醉，雌激素治疗的卵巢切除大鼠将内侧视前核（MPN）电化学刺激的（ECS），并且此后，LC、A1或A2细胞群将电刺激（ES）。这种LC或A1ES放大LH release. 其他研究将检查神经兴奋性药物是否 (e.g. 3-异丁基-甲基黄嘌呤），注入未麻醉大鼠的LC或A1区。的延髓腹外侧巨细胞旁核调节LC神经元活动，可能是通过释放兴奋性氨基酸（EAA）。将执行PGC开启的ES，以确定是否这些刺激增加下丘脑NE分泌。其他研究将评估EAA微输注到LC中是否具有在释放NE和LHRH/LH方面具有相似的兴奋作用。自从LHRH 神经元只有在特定编码的去甲肾上腺素能信号，LC或A1 ES的参数将发生变化研究这些刺激如何影响LHRH神经元的活动。由于NE可能通过GABA中间神经元起作用，下丘脑GABA神经元的作用在NE诱导的LHRH释放的调节将被检查。的阿片系统在调节NE分泌中的作用也将被研究了在这些实验中，特异性激动剂或拮抗剂 GABA或阿片受体将被置于选择性的下丘脑、中脑或后脑区及其对NE和将评估中脑或后脑ES后的LHRH分泌。 LC、A1和A2 ES后NE和LHRH分泌的变化通过HPLC和RIA对微透析获得的透析液进行评价将探针放入特定的下丘脑区域和垂体腺。 5-羟色胺（5-HT）系统也将进行研究，特别强调5-HT和NE如何相互作用，抑制LHRH神经元活性。最后，NE和5-HT相互作用与LHRH神经元在雄激素绝育和雄性大鼠是要考察这些研究将提供重要的基本信息，关于神经内分泌大脑如何发挥作用以唤起排卵前促性腺激素激增和排卵。