NEUROENDOCRINE CONTROL OF PUBERTY

青春期的神经内分泌控制

• 批准号: 6181372
• 负责人: CAROL M FOSTER
• 金额: $ 15.72万
• 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/6181372
• 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.

尽管对潜在的荷尔蒙变化进行了广泛的调查 青春期过渡，可能仍然存在关于受制者如何 面对儿童促性腺激素分泌增加的模式 性激素浓度升高表现出不同的性激素变化模式 支持月经周期和排卵的成年期。最新数据 说明男孩和女孩在青春期促性腺激素水平上有差异 分泌物。促黄体生成素的分泌似乎对性激素的反应不同 女孩的反馈与男孩相比，FSH浓度相对较低 在童年时期，女孩比男孩更少受到压抑。促性腺激素，还有 尤其是FSH，可能通过性腺多肽的变化来调节， 激活素、抑制素和卵泡抑素。对这些角色的探索 调节促性腺激素分泌的多肽一直受到阻碍，直到 现在由于缺乏具体的分析方法。在这项研究中，新的分析和 实验治疗将被用来研究的机制 女孩的青春期，测试促性腺激素分泌在 女孩会因卵巢性激素的变化而改变 卵巢多肽环境。具体地说，据假设，在 青春期对性激素的神经内分泌反应有一个开关 反馈涉及阿片类药物语气的变化和更主要的作用 脑下垂体。它还假设FSH的分泌是逐步的 被发育中的性腺分泌增加的抑制和 卵泡刺激素。这一假设将通过检查 黄体生成素、卵泡刺激素与卵巢分泌物、雌二醇抑制素A的相互作用 和B，以及卵泡抑素，在女孩的青春期：1)确定作用 雌二醇和/或孕酮在阿片类药物抑制发展中的作用 使用性类固醇替代研究的促性腺激素释放激素分泌；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)血清抑制素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 女孩的依附性和独立性性早熟。青春期导致 育龄妇女神经内分泌控制的显著变化 荷尔蒙，对这些变化的研究应该会让我们更好地理解 生殖异常和不孕不育的病理生理学。