NEUROENDOCRINOLOGY OF PUBERTY

青春期神经内分泌学

• 批准号: 6263657
• 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/6263657
• 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

This proposed research is an outgrowth of a previously awarded Clinical Research Center pilot study, Protocol 1354-P, Maturational roles of GnRH--Effects of Bromocriptine. The hypothalamic-pituitary axis is remarkably active in the fetus, but within months to 2 - 4 years after birth, depending on sex, the axis is quiescent, as if central nervous system (CNS) pathways develop to restrain hypothalamic gonadotropin- releasing hormone (GnRH) secretion. The recent recognition that GnRH neurons have receptors for dopamine, coupled with the pilot data from Protocol 1354-P, have led to our hypothesis that dopaminergic pathways restrain GnRH secretion in mid-childhood and become increasingly less active at puberty. Our pilot data indicate that bromocriptine, a dopamine agonist, produces prompt suppression of the nocturnal increase in luteinizing hormone (LH) and, by inference, GnRH secretion in pubertal boys and girls. If dopaminergic pathways are involved in restraint of pubertal GnRH secretion, then administration of dopamine antogonists should disinhibit LH secretion in pubertal children during the daytime when LH secretion is normally suppressed. 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 effectos of dopamine agonists in children and adults and by determining the acute affects of dopamine antagonists in children. The ability of bromocriptine to suppress nocturnal GnRH secretion will be determined by analysis of LH pulse frequency and amplitude from LH measurements in blood samples obtained at 10 to 20 minute intervals from 2000 to 1200h before, after one dose, and after 7 days of oral bromocruptine administration. Pituitary reserve will be assessed by administraton of exogenous GnRH at the completion of each study. The acute effects of one dose of oral metoclopramide will be determined on LH secretion between 0800 and 1200h followed by determination of pituitary responsiveness to exogenous GnRH.

这项拟议的研究是先前授予的临床研究中心试点研究，第1354-P，GNRH的成熟作用 - 溴封然的成熟作用的产物。 下丘脑 - 垂体轴在胎儿中非常活跃，但在出生后的几个月至2至4年内，根据性别，轴是静止的，好像中枢神经系统（CNS）途径发展以抑制下丘脑性促性腺泡蛋白 - 释放激素（GNRH）的分泌。最近认识到GNRH神经元具有多巴胺的受体，再加上第1354-P方案的试验数据，这使我们的假设是，多巴胺能途径在中期抑制GNRH分泌，并且在青春期越来越活跃。 我们的飞行员数据表明​​，多巴胺激动剂溴ocr诗可以迅速抑制黄体激素（LH）的夜间增加，并且通过推断，在青春期男孩和女孩中是GNRH分泌。 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Antogonists的给药应抑制青春期儿童的LH分泌。 在这项研究中，将系统探索多巴胺能CNS途径在控制青春期GNRH分泌中的作用，可以通过检查儿童和成人中多巴胺激动剂的急性和慢性作用，并确定儿童多巴胺拮抗剂的急性影响。 溴封然抑制夜间GNRH分泌的能力将通过分析LH脉冲频率和幅度分析LH测量值，从2000年到1200h，在一次剂量之前，在一次剂量之前，以及在口服溴op不平7天后，以10至20分钟的间隔获得的血液样本中的LH测量值分析。 每项研究完成时，将由外源GNRH的行政管理储备对垂体储备进行评估。一剂口服甲氧氯普胺的急性作用将在0800至1200H之间的LH分泌上确定，然后确定垂体对外源GNRH的垂体反应能力。