Central synaptic mechanisms regulating ovulation

调节排卵的中枢突触机制

• 批准号: 6995006
• 负责人: Catherine A Christian-Hinman
• 金额: $ 2.7万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6995006
• 关键词: circadian rhythms; electrophysiology; estradiol; follicle stimulating hormone; gamma aminobutyrate; genetically modified animals; glutamates; gonadotropin releasing factor; green fluorescent proteins; hormone regulation /control mechanism; laboratory mouse; luteinizing hormone; neuroendocrine system; neuroregulation; ovulation; predoctoral investigator; suprachiasmatic nucleus; vasoactive intestinal peptide; vasopressins

DESCRIPTION (provided by applicant): Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway regulating reproduction. Pulsatile GnRH release from the hypothalamus stimulates synthesis and secretion of pituitary gonadotropins. In females there is a massive surge in GnRH release that serves as the final and prerequisite signal for the pituitary luteinizing hormone (LH) surge, which subsequently initiates ovulation. The GnRH surge is dependent on 2 signals: rising ovarian estradiol levels and a daily neural signal from the suprachiasmatic nuclei (SCN). Anatomical and physiological data support roles for vasoactive intestinal polypeptide (VIP) and vasopressin in the transmission of circadian information from the SCN to GnRH neurons. The goal of this study is to determine the neurobiological mechanisms underlying the generation and timing of the GnRH surge. Specifically, electrophysiological techniques will be used to explore changes in GnRH neuron function in an animal model that exhibits daily LH surges through measurement of GnRH neuron firing rate and glutamatergic and gamma-aminobutyric acid (GABAergic) postsynaptic currents (PSCs) in GnRH neurons. Changes in response to VIP and vasopressin will help elucidate how estradiol feedback effects and the daily signal are integrated, transmitted to, and received by GnRH neurons for the proper regulation of the surge. The absolute requirement of the GnRH surge for ovulation underscores the importance of elucidating the exact mechanisms of its generation and timing.

描述（由申请人提供）：促性腺激素释放激素（GnRH）神经元形成调节生殖的最终共同途径。下丘脑脉冲性释放GnRH刺激垂体促性腺激素的合成和分泌。在女性中，GnRH释放大量激增，作为垂体促黄体生成激素（LH）激增的最终和先决条件信号，随后启动排卵。GnRH激增依赖于2个信号：卵巢雌二醇水平升高和来自视交叉上核（SCN）的日常神经信号。解剖学和生理学数据支持血管活性肠肽（VIP）和加压素在从SCN到GnRH神经元的昼夜信息传递中的作用。本研究的目的是确定GnRH激增的产生和时间的神经生物学机制。具体而言，将使用电生理学技术探索动物模型中GnRH神经元功能的变化，该动物模型通过测量GnRH神经元放电率和GnRH神经元中的谷氨酸能和γ-氨基丁酸（GABA能）突触后电流（PSC）显示每日LH激增。VIP和加压素反应的变化将有助于阐明雌二醇反馈效应和日常信号是如何整合的，传递到GnRH神经元并被其接收，以正确调节浪涌。促性腺激素释放激素激增对排卵的绝对要求强调了阐明其产生和时间的确切机制的重要性。