COITUS INDUCED C FOS EXPRESSION IN BRAINSTEM

排卵是控制生育和治疗的主要目标 不孕不育。自然排卵是通过释放大量的 下丘脑促性腺激素释放激素(GnRH)，触发 通过其他神经肽和神经递质的相互作用 (去甲肾上腺素、神经肽Y、-内啡肽、甘丙素和伽马 氨基丁酸)。这些神经化学物质存在于下丘脑中。 和/或脑干，但它们的确切位置和机械步骤 目前对GnRH分泌的调控尚不清楚。我们假设 在促性腺激素释放激素激增期间，基因转录和 表达这些化学物质的神经元的翻译也应该 增加。为了检验这一假设，我们使用了 早期癌基因c-fos作为基因启动标志的研究 转录过程。我们认为在排卵前 GnRH峰，脑干区c-fos基因表达增加 表达可能包含分泌或影响 促性腺激素释放激素激动剂的分泌。母兔是一只 检验这一假说的理想模型，因为 排卵性促性腺激素释放激素高峰可以通过与男性性交来控制。我们有 表明性交诱导的去甲肾上腺素(NE)的分泌 GnRH在10-30分钟内开始，240分钟后完成 交配。因此，启动了一项实验，在该实验中，雌性 用多聚甲醛固定兔并处死兔子 输液前及输液后30分钟、60分钟、120分钟、240分钟 性交。交配后的雄性大脑也以类似的间隔收集 用作对照，因为性交不会引起NE/GnRH升高 以美元计价。C-fos信使核糖核酸的表达正在检测中 原位杂交技术在下丘脑和下丘脑20 m切片上的应用 脑干。在交配后60分钟的女性脑干(组织在 其他时间还没有检查)，几个去甲肾上腺素 神经元区域，包括外侧被盖(A1)，丘脑的核 孤束(A2)和蓝斑(A6) C-fos基因表达增强。此外，前置词的核心 舌下腺和旁巨细胞核，仅有两个尾侧 支配蓝斑的核也表达c-fos。 交配的雌性比交配的雄性含量更高。几个 下丘脑的区域，包括弓状核和室旁核 神经肽Y、促性腺激素释放激素和甘丙肽神经元所在的核， 也表现出c-fos的表达，尽管在大小上的差异 C-fos在这些区域的表达在男性和女性之间没有 很明显。这些初步结果表明，c-fos含有 神经元可能有助于识别细胞和化学物质参与的 性交诱导的排卵前GnRH峰的早期激活。 最终，我们希望将这些研究扩展到灵长类动物，因为我们 在猕猴(Macaca Mulatta)身上观察到10倍的增长 去甲肾上腺素基因在脑干蓝斑和蓝斑的表达 下丘脑去甲肾上腺素释放大量增加 雌激素驱动的排卵前促性腺激素释放激素 涌动。我们推测，这扰乱了排卵，减少了生殖 慢性应激患者或更年期妇女的表现 可能反映了去甲肾上腺素能基因表达和活性的损伤。

Ovulation is a major target for controlling fertility and treating infertility. Natural ovulation is initiated by a surge release of hypothalamic gonadotropin-releasing hormone (GnRH), which is triggered via interaction of other neuropeptides and neurotransmitters (norepinephrine, neuropeptide Y, -endorphin, galanin and gamma aminoabutyric acid). These neural chemicals exist in the hypothalamus and/or brainstem, but their exact locations and mechanistic steps in regulating GnRH secretion is currently unknown. We hypothesize that during the GnRH surge, the magnitude of gene transcription and translation in neurons expressing these chemicals should also increase. To test this hypothesis, we utilized the expression of the early oncogene, c-fos, as a marker for the onset of gene transcriptional processes. We reasoned that during the preovulatory GnRH surge, those brainstem areas that show an increase in c-fos mRNA expression probably contain neurons that secrete, or influence secretion of, GnRH surge-inducing chemicals. The female rabbit is an ideal model to test this hypothesis because the exact timing of the ovulatory GnRH surge can be controlled by coitus with a male. We have shown that the coitally induced secretion of both norepinephrine (NE) and GnRH begins within 10-30 min and is complete by 240 min after copulation. An experiment was initiated, therefore, in which female rabbits were killed and their brains fixed by paraformaldehyde infusion at times before and 30 min, 60 min, 120 min and 240 min after coitus. Mated male brains were also collected at similar intervals for use as controls because coitus does not induce NE/GnRH increases in the buck. Expression of c-fos mRNA is being examined by the in situ hybridization technique in 20 m sections of the hypothalamus and brainstem. In the female brainstem at 60 min after coitus (tissues at other times have not yet been examined), several noradrenergic neuronal areas, including the lateral tegmentum (A1), the nucleus of the solitary tract (A2) and the locus coeruleus (A6), exhibited enhanced c-fos mRNA expression. Moreover, the nucleus of prepositus hypoglossy and the paragigantocellular nucleus, the only two caudal nuclei that innervate the locus coeruleus, also expressed c-fos in higher content in the mated female than in the mated male. Several areas in the hypothalamus, including the arcuate and paraventricular nuclei where neuropeptide Y, GnRH and galanin neurons are located, also exhibited c-fos expression, although differences in the magnitude of c-fos expression in these areas between males and females were not apparent. These preliminary results suggest that c-fos containing neurons may be useful in identifying cells and chemicals involved in early activation of the coitus-induced preovulatory GnRH surge. Ultimately, we hope to extend these studies to primates because we have observed in the monkey (Macaca mulatta) that a 10-fold increase in norepinephrine gene expression in the brainstem locus coeruleus and a massive increase in hypothalamic norepinephrine release occur immediately before and during the estrogen-driven preovulatory GnRH surge. We speculate that disrupted ovulation and reduced reproductive performance in patients under chronic stress or in menopausal women may reflect a lesion in noradrenergic gene expression and activity.