NEUROENDOCRINOLOGY OF PUBERTY

青春期神经内分泌学

• 批准号: 6303444
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6303444
• 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.

下丘脑垂体在胎儿中非常活跃，但是在出生后的几个月内，轴是静止的，好像中枢神经系统（CNS）途径发展为抑制下丘脑性促性腺激素释放激素（GNRH）分泌。 在青春期，这种约束开始在晚上，然后在白天开始消失。最近认识到GNRH神经元具有多巴胺受体的认识，导致了我们的假设，即多巴胺能途径抑制了年龄中期的GNRH分泌，并且在青春期越来越活跃。 如果多巴胺能途径涉及青春期GNRH分泌的约束，则在通常抑制LH分泌的白天，多巴胺拮抗剂的给药应抑制青春期儿童的LH分泌。 相反，当它在青春期儿童中最活跃时，多巴胺激动剂应该能够减少LH分泌。在这项研究中，通过检查多巴胺激动剂在儿童和成人中的急性和慢性作用，通过确定儿童多巴胺拮抗剂的急性影响，对多巴胺能CNS途径在控制青春期GNRH分泌中的作用进行系统探索。 最初，在8个男孩和8个女孩中，将确定多巴胺激动剂溴封然的急性和持续抑制的能力。 平行研究将在8名男性和8名女性中进行，以确定多巴胺能系统在成年人中保持活跃的程度。 从下丘脑中释放GnRH会导致外周血的LH浓度升高。 因此，将从经常获得的血液样本中的LH测量结果确定溴o不平抑制夜间GNRH分泌的能力。在这项研究之后，有8个男孩和8个女孩将接受多巴胺拮抗剂甲氧氯普胺，以确定其在青春期儿童中抑制白天抑制LH脉搏频率和振幅的能力。 这些研究将扩大我们对控制青春期时机和节奏的中枢神经系统途径的了解。