NEUROENDOCRINE CONTROL OF PUBERTY

青春期的神经内分泌控制

• 批准号: 2888862
• 负责人: CAROL M FOSTER
• 金额: $ 15.26万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2888862
• 关键词: adolescence (12-20); age difference; clinical research; estradiol; female; follicle stimulating hormone; follistatin; gonadotropin releasing factor; hormone regulation /control mechanism; human puberty; human subject; hypogonadism; hypopituitarism; hypothalamic pituitary axis; inhibin; luteinizing hormone; menstrual cycle; middle childhood (6-11); naloxone; neuroendocrine system; pituitary gonadal axis; progesterone; secretion; sex hormones; steroid hormone biosynthesis

Despite extensive investigation of the hormonal changes underlying the pubertal transition, may questions remain regarding how the restrained pattern of childhood gonadotropin secretion increased in the face of rising sex steroid concentrations to exhibit the variable patterns of adulthood that support menstrual cyclicity and ovulation. Recent data indicate that boys have girls have differences in pubertal gonadotropin secretion. LH secretion appears to respond differently to sex steroid feedback in girls compared to boys, and FSH concentrations are relatively less suppressed in childhood in girls than in boys. The gonadotropins, and particularly FSH, may be regulated in changes in the gonadal peptides, activin, inhibin and follistatin. Exploration of the roles of these peptides in regulation of gonadotropin secretion has been hampered until now by lack of specific assays. In this research, novel assays and experimental treatments will be employed to investigate the mechanisms of puberty in girls, testing the hypothesis that gonadotropin secretion in girls is altered in response to the changing ovarian sex steroid and ovarian peptide milieu. Specifically, it is hypothesized that, during puberty there is a switch in the neuroendocrine responses to sex steroid feedback involving changes in opioid tone and a more predominant role of the pituitary. It is also hypothesized that FSH secretion is progressively inhibited by the developing gonad's increasing secretion of inhibition and follistatin. The hypothesis will be evaluated by examining the interactions of LH, FSH and the ovarian secretions, estradiol inhibin A and B, and follistatin, during puberty in girls: 1) determining the role of estradiol and/or progesterone in the development of opioid inhibition of GnRH secretion using sex steroid replacement studies; 2) examining the changes in hypothalamic and pituitary sensitivity to estradiol between adult women and pubertal girls; 3) relating changes in serum inhibin A and B, activin A, and follistatin concentrations to serum gonadotropin and sex steroid concentrations to serum FSH concentrations during gonadotropin- dependent and independent precocious puberty in girls. Puberty results in remarkable changes in the neuroendocrine control of the reproductive hormones, and study of these changes should lead to a better understanding of the pathophysiology of reproductive abnormalities and infertility.

尽管广泛的调查荷尔蒙的变化背后的 青春期的过渡，可能仍然存在的问题，关于如何克制 儿童促性腺激素分泌增加的模式，在面对 性类固醇浓度升高， 支持月经周期和排卵。最近的数据 表明男孩和女孩在青春期促性腺激素方面存在差异 分泌物LH分泌似乎对性类固醇有不同的反应 与男孩相比，女孩的反馈，FSH浓度相对 女孩在童年时期受到的压抑比男孩少。促性腺激素， 特别是FSH，可能在性腺肽的变化中受到调节， 激活素、促卵泡素和卵泡抑素。对这些角色的探索 促性腺激素分泌的调节肽已经受到阻碍， 现在缺乏具体的分析。在这项研究中， 将采用实验治疗来研究 青春期女孩，测试的假设，促性腺激素分泌， 女孩的卵巢性类固醇的变化会改变， 卵巢肽环境。具体而言，假设在 青春期有一个开关在神经内分泌反应性类固醇 反馈涉及阿片样物质张力的变化， 脑垂体还假设FSH分泌是渐进性的， 受发育中的性腺分泌抑制的增加所抑制， 卵泡抑素 该假设将通过检查 LH、FSH与卵巢分泌物、雌二醇、卵泡抑素A的相互作用 和B，卵泡抑素，在青春期的女孩：1）确定的作用， 雌二醇和/或孕酮在阿片类药物抑制发展中的作用 促性腺激素释放激素分泌使用性类固醇替代研究; 2）检查 下丘脑和垂体对雌二醇敏感性的变化， 成年妇女和青春期女孩; 3）血清中的白蛋白A和 B、激活素A和卵泡抑素浓度与血清促性腺激素和性别的关系 促性腺激素期间类固醇浓度与血清FSH浓度的关系- 女孩的依赖性和独立性早熟。青春期导致 生殖神经内分泌控制的显著变化 激素，对这些变化的研究应该会导致更好的理解 生殖异常和不育的病理生理学。