NEUROENDOCRINOLOGY OF PUBERTY

青春期神经内分泌学

• 批准号: 6297014
• 负责人: CAROL M FOSTER
• 金额: $ 0.02万
• 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: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6297014
• 关键词: adult human (21+); bioperiodicity; blood chemistry; bromocriptine; central nervous system; child (0-11); dopamine receptor; gender difference; gonadotropin releasing factor; hormone biosynthesis; human puberty; human subject; neuroendocrine system; neuroregulation; receptor expression

The hypothalamic-pituitary axis is remarkably active in the fetus, but within months after birth, the axis is quiescent, as if central nervous system (CNS) pathways develop to restrain hypothalamic gonadotropin-releasing hormone (GnRH) secretion. At puberty, this restraint begins to disappear, first at night, and then in the daytime. The recent recognition that GnRH neurons have receptors for dopamine have led to our hypothesis that dopaminergic pathways restrain GnRH secretion in mid-childhood and become increasingly less active at puberty. If dopaminergic pathways are involved in restraint of pubertal GnRH secretion, then administration of dopamine antagonists should disinhibit LH secretion in pubertal children during the daytime when LH secretion is normally suppressed. Conversely, dopamine agonists should be able to decrease LH secretion at night, when it is most active in pubertal children. In this research, a systematic exploration of the role of dopaminergic CNS pathways in the control of pubertal GnRH secretion will be undertaken by examining acute and chronic effects of dopamine agonists in children and adults and by determining the acute effects of dopamine antagonists in children. Initially, the ability of the dopamine agonist, bromocriptine, to produce acute and sustained suppression of GnRH secretion will be determined in 8 boys and 8 girls. Parallel studies will be carried out in 8 men and 8 women to determine to what degree the dopaminergic system remains active in adults. Release of GnRH from the hypothalamus results in an increase of LH concentration in peripheral blood. Thus, the ability of bromocriptine to suppress nocturnal GnRH secretion will be determined from LH measurements in blood samples obtained frequently. Following this study 8 boys and 8 girls will receive the dopamine antagonist, metoclopramide, to determine its ability to disinhibit the daytime suppression of LH pulse frequency and amplitude seen in pubertal children. These studies will expand our knowledge of the CNS pathways that control the timing and tempo of puberty.

胎儿的下丘脑-脑垂体轴非常活跃，但在出生后几个月内，该轴处于静止状态，似乎中枢神经系统(CNS)途径的发展抑制了下丘脑促性腺激素释放激素(GnRH)的分泌。在青春期，这种束缚开始消失，首先是在晚上，然后是白天。最近对GnRH神经元具有多巴胺受体的认识导致了我们的假设，即多巴胺能途径在童年中期抑制GnRH的分泌，并在青春期变得越来越不活跃。如果多巴胺能途径参与抑制青春期促性腺激素释放激素的分泌，那么在青春期儿童黄体生成素分泌通常被抑制的白天，使用多巴胺拮抗剂应该不会抑制黄体生成素的分泌。相反，多巴胺激动剂应该能够减少夜间黄体生成素的分泌，而此时青春期儿童的黄体生成素最活跃。在这项研究中，将通过检测多巴胺激动剂对儿童和成人的急性和慢性影响以及通过确定多巴胺拮抗剂对儿童的急性影响来系统地探索多巴胺能中枢神经系统通路在青春期GnRH分泌控制中的作用。最初，将在8名男孩和8名女孩身上测定多巴胺激动剂溴隐亭产生急性和持续抑制GnRH分泌的能力。将对8名男性和8名女性进行平行研究，以确定成年人的多巴胺能系统在多大程度上保持活跃。下丘脑释放促性腺激素释放激素导致外周血中促黄体生成素浓度升高。因此，溴隐亭抑制夜间促性腺激素释放激素分泌的能力将通过经常获得的血液样本中的促黄体生成素测定来确定。在这项研究之后，8名男孩和8名女孩将接受多巴胺拮抗剂甲氧氯普胺，以确定其抑制青春期儿童白天出现的促黄体生成素脉冲频率和幅度抑制的能力。这些研究将扩大我们对控制青春期时间和节奏的中枢神经系统通路的了解。