NEUROCHEMICAL & ANATOMICAL STEPS IN PREOVULATORY GNRH RELEASE

神经化学

• 批准号: 6453706
• 负责人: HAROLD G SPIES
• 金额: $ 11.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6453706
• 关键词: Mammalia; clinical research; endocrine gland /system; hormones; nervous system; structural biology; women's health

Ovulation is a major target for the control of fertility and infertility in humans and animals. Several neuropeptides and neurotransmitters, i.e., neuropeptide Y, b-endorphin, norepinephrine (NE), gamma aminobutyric acid and acetylcholine, influence the preovulatory secretion pattern of gonadotropin-releasing hormone (GnRH). The magnitude of gene transcription/translation in the neurons that express these chemicals may identify how and where they modulate GnRH release. To test this hypothesis, we utilized the expression of the early oncogene, cfos, as a marker to locate the onset of gene transcriptional events in brainstem and hypothalamus during the preovulatory GnRH surge. Coitus in female rabbits, like estrogen in monkeys, induces NE/GnRH release at a predicted time after the stimulus. Thus, rabbits were killed and their brains fixed by paraformaldehyde infusion at times before and 15-, 30-, 60-, 90- and 120-min after coitus for cfos mRNA quantitation using in s itu hybridization. Within 30 minutes after coitus, several noradrenergic-associated brainstem nuclei, lateral tegmentum (A1), nucleus of the solitary tract (A2) and locus coeruleus (A6) exhibited enhanced cfos mRNA expression in females. Also, two nuclei in the medulla oblongata that send projections to A6, the nucleus of praepositus hypoglossy and the paragigantocellular nucleus, showed increased c-fos expression only in coitally activated females. The septum also showed heavier 35S-cfos label by 30 min after coitus than septum from unmated control females. In the hypothalamus the anteroventral periventricular area (AVPV), arcuate, paraventricular and medial preoptic area showed enhanced cfos mRNA expression between 15 and 60 minutes postmating. The AVPV showed the most concentrated cfos expression. Whether these times after coitus and transcriptional changes in cfos signals can be utilized for predictions of where and how coital stimulation triggers NE/GnRH release is unclear, but these data are encouraging. Because a massive release of hypothalamic NE and a two-fold increase in brainstem NE (A6) gene expression occurred around the time of the estrogen-induced hypothalamic GnRH release, we suggest that the signaling mechanisms in rabbits may be useful in understanding those in primates. FUNDING NIH HD30316, HD18185 PUBLICATIONS None

排卵是控制生育的主要目标， 人类和动物的不孕症。 几种神经肽和 神经递质，即，神经肽Y、b-内啡肽、去甲肾上腺素 (NE)，γ-氨基丁酸和乙酰胆碱，影响 促性腺激素释放激素排卵前分泌型 （GnRH）。 基因转录/翻译的幅度在 表达这些化学物质的神经元可以识别它们如何以及在哪里表达这些化学物质。 调节GnRH释放。 为了验证这一假设，我们使用了 早期癌基因cfos的表达，作为一个标记，以定位 脑干和下丘脑基因转录事件的发生 在排卵前GnRH激增期间。 雌兔交媾，比如 雌激素在猴子中，诱导NE/GnRH释放在预测的时间后 刺激计划 因此，兔子被杀死，他们的大脑被固定， 在15、30、60、90和 120-交配后1 min，采用原位杂交法定量c-fos mRNA 杂交方法 性交后30分钟内， 去甲肾上腺素相关脑干核，外侧被盖（A1）， 孤束核（A2）和蓝斑核（A6）显示 增强雌性c-fos mRNA表达。 此外，两个原子核在 延髓发出投射到A6， praepositus hypoglossy和paragigantocellular核，显示 c-fos表达仅在性交激活的雌性中增加。 的 在性交后30 min，隔膜也显示出较重的35 S-cfos标记， 未交配对照雌性的隔膜。 在下丘脑， 前腹侧室周区（AVPV），弓形，室旁 和内侧视前区c-fos mRNA表达增强， 交配后15和60分钟。 AVPV表现出最集中的 cfos表达。 在性交和转录后的这些时间 CFOS信号的变化可用于预测 性交刺激如何触发NE/GnRH释放尚不清楚，但这些 数据令人鼓舞。 因为下丘脑NE的大量释放 脑干NE（A6）基因表达增加了两倍， 在雌激素诱导下丘脑GnRH释放的时间前后，我们 表明兔子的信号机制可能有助于 了解灵长类动物的基因。 资助NIH HD 30316、HD 18185 出版物