Ovarian Hormone Regulation of LHRH Biosynthesis

LHRH 生物合成的卵巢激素调节

基本信息

批准号：
8099322
负责人：
SANDRA L PETERSEN
金额：
$ 8.63万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8099322
关键词：
Adenylate Cyclase Aging Agonist Animals Anteroventral Thalamic Nucleus Brain region Cell Nucleus Cells Cyclic AMP Data Equilibrium Estradiol Estrogens Female Gene Expression Glutamate Decarboxylase Glutamate Transporter Glutamates Gonadotropin Hormone Releasing Hormone Green Fluorescent Proteins Human Hypothalamic structure Infertility Lead Ligands Light Link Measures Mediating Messenger RNA Modeling Mus Nerve Degeneration Neurons Neuropeptides Neurotensin Neurotransmitters Norepinephrine Ovarian Ovarian hormone Ovulation Pattern Peptides Phenotype Photoperiod Preoptic Areas Principal Investigator Progesterone Receptors Puberty Rattus Research Rosa Signal Transduction Steroids Structure Testing Time Transgenic Organisms Vasoactive Intestinal Peptide Vasoactive Intestinal Peptide Receptors Vasopressin Receptor Vasopressins Work base gamma-Aminobutyric Acid hormone biosynthesis hormone regulation immunocytochemistry inhibitor/antagonist insight nerve supply neurodevelopment neuronal cell body neuroprotection neurotransmission nonhuman primate novel premature prevent programs receptor relating to nervous system sex suprachiasmatic nucleus transmission process vesicular GABA transporter vesicular glutamate transporter 2

项目摘要

The long-term objective of this research is to determine how ovarian steroids trigger luteinizing hormone-releasing hormone (LHRH) and LH surge release, thereby inducing ovulation. In these studies, we will investigate mechanisms through which potoperiod and estrogen signals interact to regulate novel dual-phenotype GABA/glutamate neurons in the anteroventral periventricular nucleus (AVPV) of females. The specific aims of this proposal are: 1) To verify that GABA/glutamate neurons communicate directly with LHR neurons we will use anterograde and retrograde tracing and immunocytochemistry in rats and mice; 2) We will use electrophysiological studies in which LHRH neurons are identified by GGP expression to verify that AVPV GABA/Glutamate neurons release predominantly GABA during the morning and predominantly glutamate in the afternoon; 3) To determine whether vasopressin (VP) and/or noradrenaline (NA) trigger the midday rise in GABA release linked to the LH surge. We will examine the effects of specific VP and NA receptor antagonists on expression of a marker of GABA release, glutamic acid decarboxylase 67 (GAD67) mRNA. We will also determine whether changes in GAD67 mRNA levels are blocked when animals are placed in constant light and if such changes, as well as LH surge release, can be induced with VP and/or NA receptor agonists; 4) To determine whether autofeedback inhibits GABA synthesis while stimulating glutamate release prior to the LH surge, we will administer GABAB receptor antagonists and measure changes in GAD67 mRNA levels in AVPV cell bodies, as well as vesicular GABA transporter and vesicular glutamate transporter in dual-phenotype terminals contacting LHRH neurons; 5) We will determine whether VIP stimulates cAMP-dependent NT gene expression through ligand-independent activation of PR on the afternoon of the LH surge. The results of these studies may provide new targets for examination in humans and nonhuman primates and may lead to a better understanding of the neural aspects of puberty, infertility and hypothalamic aging. In addition, establishing that GABA neurons are able to switch from inhibitory neurotransmission to excitatory transmission will have important implications for understanding GABA and glutamatergic "dual-signaling" in other brain regions. Finally, the results of these studies may provide key insights into how E2 regulates such diverse functions as sex-specific neurodevelopment, neuroprotection and neurodegeneration

这项研究的长期目标是确定卵巢类固醇如何触发黄体化激素释放激素（LHRH）和LH激增释放，从而诱导排卵。在这些研究中，我们将研究 Potoperiod 和雌激素信号相互作用以调节新的机制女性前腹侧室周核（AVPV）中的双表型 GABA/谷氨酸神经元。该提案的具体目标是：1）验证 GABA/谷氨酸神经元直接与 LHR 神经元我们将在大鼠和小鼠中使用顺行和逆行追踪和免疫细胞化学； 2）我们将使用通过 GGP 表达来识别 LHRH 神经元的电生理学研究来验证 AVPV GABA/谷氨酸神经元在早上主要释放 GABA，并且主要下午吃谷氨酸； 3) 确定加压素 (VP) 和/或去甲肾上腺素 (NA) 是否触发中午 GABA 释放量的上升与 LH 激增有关。我们将检查特定 VP 和 NA 的影响受体拮抗剂对 GABA 释放标志物谷氨酸脱羧酶 67 (GAD67) 表达的影响 mRNA。我们还将确定当动物被置于恒定光照下，如果可以用 VP 和/或 NA 诱导此类变化以及 LH 激增释放受体激动剂； 4) 确定自动反馈在刺激时是否抑制GABA合成 LH 激增之前谷氨酸释放，我们将施用 GABAB 受体拮抗剂并测量 AVPV 细胞体以及囊泡 GABA 转运蛋白和囊泡中 GAD67 mRNA 水平的变化双表型末端接触 LHRH 神经元的谷氨酸转运蛋白； 5）我们将确定是否 VIP 通过不依赖配体的 PR 激活来刺激 cAMP 依赖性 NT 基因表达下午 LH 激增。这些研究结果可能为人体检查提供新的目标和非人类灵长类动物，可能有助于更好地理解青春期、不孕不育的神经方面和下丘脑老化。此外，确定 GABA 神经元能够从抑制状态转变为神经传递到兴奋性传递对于理解 GABA 和其他大脑区域的谷氨酸“双重信号”。最后，这些研究的结果可能提供关键深入了解 E2 如何调节性别特异性神经发育、神经保护等多种功能和神经退行性变