EFFECT OF PROGESTERONE ON GONADOTROPIN SECRETION

黄体酮对促性腺激素分泌的影响

• 批准号: 2197344
• 负责人: VIRENDRA B MAHESH
• 金额: $ 15.76万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2197344
• 关键词: GABA receptor; endorphins; estrogen receptors; estrogens; follicle stimulating hormone; gamma aminobutyrate; glutamate decarboxylase; gonadotropin releasing factor; gonadotropins; hormone inhibitor; hormone regulation /control mechanism; hypothalamus; laboratory rat; luteinizing hormone; mifepristone; neuropeptide Y; opioid receptor; ovariectomy; pituitary gland; progesterone; progesterone receptors; proopiomelanocortin; receptor binding; secretion; tissue /cell culture

Significant progress has been made during the last 5 years in elucidating the complex mechanisms involved in the stimulatory and inhibitory effects of progesterone on gonadotropin secretion. From these studies, a multifactorial hypothesis explaining regulation of gonadotropin secretion by progesterone has been proposed which includes progesterone regulation of estrogen receptor dynamics, modulation of opioid tone, and modulation of GABA and glutamate neurotransmission of the positive and negative feedback effects of progesterone. This renewal application will further elucidate mechanisms involved with the initiation and termination of the gonadotropin surge and has 4 specific aims. SPECIFIC AIM 1 will determine the mechanism of an increase in estrogen receptors of the pituitary associated with the termination of the preovulatory gonadotropin surge. The study will include measurement of pituitary ER mRNA transcription and translation along with ER binding and degradation. The role of a hypothalamic factor will also be investigated by using hypothalamic-lesioned rats, a GnRH antagonist and NPY. SPECIFIC AIM 2 will determine the role of estrogens and progesterone on the regulation of the opioid tone during the gonadotropin surge. The studies will include the measurement of hypothalamic beta-endorphin, opioid receptors and POMC mRNA levels and their correlation with gonadotropin secretion. SPECIFIC AIM 3 will determine the role of GABA in progesterone-induced inhibition and stimulation of gonadotropin secretion in the hypothalamus and the pituitary. The study will use in vitro hypothalamic GnRH release and pituitary FSH and LH release in the presence and absence of GABA agonists and antagonists and intraventricular injection of GABA antagonists. GABA receptors will also be measured. SPECIFIC AIM 4 will determine the role of glutamic acid decarboxylase (GAD) in the stimulation and suppression of gonadotropin secretion by progesterone. The study will include measurement of hypothalamic GnRH, GABA, glutamic acid, GAD activity and GAD mRNA levels during progesterone induced stimulation and suppression of gonadotropin secretion. These studies will provide new information on the neuroendocrine regulation of gonadotropin secretion by progesterone.

过去 5 年在阐明这一问题方面取得了重大进展 刺激和抑制作用涉及的复杂机制 黄体酮对促性腺激素分泌的影响。 从这些研究中， 解释促性腺激素分泌调节的多因素假说 已提出由孕酮调节，其中包括孕酮调节 雌激素受体动力学、阿片类药物张力的调节和调节 GABA 和谷氨酸神经传递的正负 黄体酮的反馈作用。 此次续签申请将进一步 阐明与启动和终止有关的机制 促性腺激素激增，有 4 个具体目标。 具体目标 1 将 确定雌激素受体增加的机制 垂体与排卵前的终止有关 促性腺激素激增。 该研究将包括垂体 ER 的测量 mRNA 转录和翻译以及 ER 结合和降解。 下丘脑因子的作用也将通过使用进行研究 下丘脑损伤的大鼠，GnRH 拮抗剂和 NPY。 具体目标 2 将决定雌激素和孕激素在调节中的作用 促性腺激素激增期间阿片类药物的浓度。 这些研究将 包括测量下丘脑β-内啡肽、阿片受体 和 POMC mRNA 水平及其与促性腺激素分泌的相关性。 具体目标 3 将确定 GABA 在黄体酮诱导的 抑制和刺激下丘脑促性腺激素分泌 和垂体。 该研究将利用体外下丘脑 GnRH 释放 以及 GABA 存在和不存在时垂体 FSH 和 LH 的释放 激动剂和拮抗剂以及脑室内注射 GABA 对手。 GABA 受体也将被测量。 具体目标 4 将 确定谷氨酸脱羧酶 (GAD) 在 黄体酮刺激和抑制促性腺激素分泌。 该研究将包括测量下丘脑 GnRH、GABA、谷氨酸 黄体酮诱导期间的酸、GAD 活性和 GAD mRNA 水平 刺激和抑制促性腺激素分泌。 这些研究 将为神经内分泌调节提供新的信息 黄体酮分泌促性腺激素。