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.

尽管对荷尔蒙变化的广泛研究 青春期的过渡，可能会遇到有关约束方式的问题 面对儿童促性腺激素分泌的模式增加了 性类固醇浓度上升以表现出可变模式 支持月经循环和排卵的成年。最新数据 表明男孩有女孩在青春期促性腺激素有差异 分泌。 LH分泌似乎对性类固醇的反应不同 与男孩相比，女孩的反馈和FSH浓度相对 与男孩相比，女孩对童年时代的压制少。促性腺激素和 特别是FSH，可以在性腺肽的变化中调节， 激活素，抑制素和卵泡素。探索这些角色 促性腺激素分泌调节中的肽一直受到阻碍 现在由于缺乏特定的测定。在这项研究中，新颖的测定和 将采用实验治疗来研究 女孩的青春期，检验了促性腺激素分泌的假设 响应不断变化的卵巢性类固醇和 卵巢肽环境。具体来说，假设在 青春期神经内分泌对性类固醇的反应 反馈涉及阿片类药物张力的变化和更为主要的作用 垂体。还假设FSH分泌逐渐 受到性腺发展的抑制和分泌的抑制 follistatin。 该假设将通过检查 LH，FSH和卵巢分泌物的相互作用，雌二醇抑制素A 和B，以及follistatin，在女孩的青春期中：1）确定角色 雌二醇和/或孕酮的阿片类药物抑制作用 使用性类固醇替代研究的GnRH分泌； 2）检查 下丘脑和垂体对雌二醇的敏感性的变化 成年女性和青春期女孩； 3）有关血清抑制素A的变化和 B，激活素A和卵泡蛋白浓度为血清促性腺激素和性别 促性腺激素期间血清FSH浓度的类固醇浓度 女孩的依赖和独立的早熟青春期。青春期导致 生殖神经内分泌控制的显着变化 激素和对这些变化的研究应导致更好的理解 生殖异常和不育的病理生理学。