PHYSIOLOGICAL REGULATION OF GONADOTROPIN GENE EXPRESSION

描述（改编自研究者摘要）：目的 本申请旨在阐明导致 FSH和LH的差异分泌。 第一个具体目标将测试 假设特定的GnRH脉冲模式的能力， 差异刺激FSHb和FSH分泌是由 垂体激活素和卵泡抑制素（FS）。 最初的实验将使用 GnRH缺乏的体内模型，以检查GnRH脉冲模式的影响 和性腺类固醇激素对B-bB、B-a和FSHb mRNA水平的影响， FSH分泌。 接下来的实验将使用体内和体外 应用肽和抗血清测试垂体FS的作用， 激活素介导GnRH对FSH合成和分泌的作用。 的 在这个特定目标的最后研究将检查激素的作用， 通过监测垂体的影响，免疫中和的阿托伐他汀， 并测试假设，睾丸激素阻止的行动， 通过给女性睾丸激素和男性抗雄激素来治疗睾丸激素。 的 第二个具体目标将利用RT-PCR测量原发性 评估GnRH脉冲模式和性腺激素的影响 对FSHb和LHb基因的转录速率的影响，使用相同的体内 具体目标1。

DESCRIPTION (Adapted from the Investigator's Abstract): The objective of this application is to elucidate the mechanisms responsible for the differential secretion of FSH and LH. The first specific aim will test the hypothesis that the ability of specific GnRH pulse patterns to differentially stimulate FSHb and FSH secretion is mediated by changes in pituitary activin and follistatin (FS). The initial experiments will use a GnRH-deficient in vivo model to examine the effects of GnRH pulse patterns and gonadal steroids on mRNA levels of inhibin-bB, inhibin-a, and FSHb and FSH secretion. The next experiments will use in vivo and in vitro application of peptides and antisera to test the role of pituitary FS and activin in mediating the action of GnRH on FSH synthesis and secretion. The final studies in this specific aim will examine the hormonal role of inhibin by monitoring the pituitary effects of immunoneutralization of inhibin in females and test the hypothesis that testosterone blocks that action of inhibin by giving testosterone to females and anti-androgens to males. The second specific aim will make use of RT-PCR measurements of primary transcripts to assess the effect of GnRH pulse patterns and gonadal hormones on the transcription rate of the FSHb and LHb genes, using the same in vivo models as Specific Aim 1.