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研究 青春期过渡，可能仍然存在关于如何克制的问题 儿童期促性腺激素分泌模式增加 性类固醇浓度上升以表现出不同的模式 成年期支持月经周期和排卵。近期数据 表明男孩与女孩青春期促性腺激素存在差异 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，FSH 浓度相对较低 女孩在童年时期的压抑程度低于男孩。促性腺激素，和 特别是 FSH，可能会通过性腺肽的变化进行调节， 激活素、抑制素和卵泡抑素。探索这些角色的作用 肽对促性腺激素分泌的调节一直受到阻碍，直到 现在由于缺乏具体的测定。在这项研究中，新颖的分析方法和 将采用实验治疗来研究其机制 女孩的青春期，检验促性腺激素分泌的假设 女孩会因卵巢性类固醇的变化而发生变化， 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发生了转变 反馈涉及阿片类药物基调的变化和更主要的作用 垂体。还假设 FSH 的分泌是逐渐进行的。 受发育中性腺分泌的抑制物的增加所抑制 卵泡抑素。 该假设将通过检查来评估 LH、FSH 和卵巢分泌物、雌二醇抑制素 A 的相互作用 B 和卵泡抑素，在女孩青春期：1) 确定作用 雌二醇和/或黄体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研究 GnRH 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的相关变化和 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 促性腺激素分泌期间类固醇浓度与血清 FSH 浓度的关系 女孩依赖性和独立性性早熟。青春期的结果是 生殖神经内分泌控制发生显着变化 激素，对这些变化的研究应该可以更好地理解 生殖异常和不孕症的病理生理学。