REGULATION OF FSH SECRETION BY THE PERIFUSED PITUITARY GLAND

周围垂体对 FSH 分泌的调节

• 批准号: 3842846
• 负责人: NEENA B SCHWARTZ
• 金额: --
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3842846
• 关键词: cell cell interaction; corticosterone; cortisol; estradiol; follicle stimulating hormone; glucocorticoids; gonadotropin releasing factor; gonadotropins; hormone biosynthesis; hormone receptor; hormone regulation /control mechanism; inhibin; laboratory rat; luteinizing hormone; male castration; ovariectomy; pituitary gland; progesterone; radioimmunoassay; secretion; sex cycle; testosterone; tissue /cell culture

The long term objective of the experiments in this project is to discover which aspects of differential FSH and LH release are regulated directly at the level of the anterior pituitary gland itself. Three in vitro setups will be used: (a) a dynamic perifusion apparatus using dispersed cells; (b) a dynamic perifusion apparatus using pituitary fragments; (c) a static, dispersed pituitary cell culture. These set-ups will permit contrast of dynamic vs static GnRH input-gonadotrope-output relations as well as contrast of dynamic control in the absence (dispersed) and presence (pituitary fragments)) of cell-cell connections. We will measure LH and FSH in the medium and in the pituitary gland, as well as pituitary GnRH receptor levels. Specific Aim 1 is to examine FSH and LH secretory rates in response to variations in intensity, duration and/or frequency of GnRH input, frequently cited as accounting for differences in the secretion rates of the two gonadotropins. Donors will be intact males and intact females at each cycle stage. Specific Aim 2 is to determine the effect of in vitro treatment with gonadal steroids and folliculostatin on FSH and LH secretion in basal and GnRH-stimulated pituitaries. The literature is contradictory on the site(s) of gonadal negative feedback; our models will enable us to probe for interactions between these feedback factors and a dynamic GnRH signal, at the level of the pituitary gland itself. Specific Aim 3 is to determine the effect of in vivo increases or decreases in gonadal feedback in donor males and females on the secretory activity in vitro of their pituitaries. Specific Aim 4 is to determine whether the anterior pituitary gland itself is an important site of interaction of glucorticoids on differential regulation of LH and FSH secretion rates. In vivo, castrated male rats pretreated with cortisol show a suppressed LH response to GnRH, but the FSH secretory response to GnRH is normal, and pituitary FSH stores are increased, suggesting that glucocorticoids could be an important probe in the search for the site of differential FSH regulation. This finding could not be replicated in a static, dispersed pituitary cell culture.

该项目实验的长期目标是 发现 FSH 和 LH 释放差异的哪些方面 直接在垂体前叶水平调节 本身。 将使用三种体外设置：（a）动态灌注 使用分散细胞的装置； (b) 动态灌注装置 使用垂体碎片； (c) 静态、分散的垂体细胞 文化。 这些设置将允许动态与静态的对比 GnRH 输入-促性腺激素-输出关系以及对比 不存在（分散）和存在（垂体）的动态控制 片段））细胞与细胞的连接。 我们将测量 LH 和 培养基和垂体中的 FSH，以及垂体 GnRH 受体水平。 具体目标 1 是检查 FSH 和 LH 分泌率随强度、持续时间的变化而变化 和/或 GnRH 输入的频率，经常被引用为会计 两种促性腺激素分泌率的差异。 每个周期的供体将是完整的雄性和完整的雌性 阶段。 具体目标 2 是确定体外的效果 使用性腺类固醇和卵泡抑素治疗 FSH 和 LH 基础垂体和 GnRH 刺激垂体的分泌。 这 关于性腺阴性位点的文献是相互矛盾的 反馈;我们的模型将使我们能够探索相互作用 在这些反馈因素和动态 GnRH 信号之间， 垂体本身的水平。 具体目标 3 是 确定体内性腺增加或减少的影响 男性和女性捐赠者对分泌活动的反馈 他们的垂体体外。 具体目标 4 是确定是否 垂体前叶本身就是一个重要的部位 糖皮质激素对 LH 和 LH 差异调节的相互作用 FSH 分泌率。 在体内，阉割的雄性大鼠经过预处理 皮质醇显示出 LH 对 GnRH 的抑制反应，但 FSH 对 GnRH 的分泌反应正常，垂体 FSH 储存 增加，表明糖皮质激素可能是一种 寻找差异 FSH 位点的重要探针 规定。 这一发现无法在静态、 分散的垂体细胞培养物。