NEUROENDOCRINOLOGY OF PUBERTY

下丘脑-垂体轴在胎儿时期非常活跃，但在出生后的几个月内，该轴是静止的，好像中枢神经系统（CNS）通路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，这种约束开始消失，首先在晚上，然后在白天。最近认识到GnRH神经元具有多巴胺受体，这导致我们假设多巴胺能通路在儿童中期抑制GnRH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青春期GnRH分泌的抑制，那么在LH分泌通常受到抑制的白天，给予多巴胺拮抗剂应该会抑制青春期儿童的LH分泌。 相反，多巴胺受体激动剂应该能够减少LH分泌在夜间，当它是最活跃的青春期儿童。在这项研究中，多巴胺能中枢神经系统通路在青春期GnRH分泌控制的作用进行了系统的探索，通过检查急性和慢性的影响，多巴胺受体激动剂在儿童和成人，并通过确定多巴胺拮抗剂在儿童的急性影响。 首先，将在8名男孩和8名女孩中确定多巴胺激动剂溴隐亭对GnRH分泌产生急性和持续抑制的能力。 将在8名男性和8名女性中进行平行研究，以确定多巴胺能系统在成年人中保持活跃的程度。 下丘脑释放GnRH导致外周血LH浓度升高。 因此，溴隐亭抑制夜间GnRH分泌的能力将通过频繁采集的血液样本中的LH测量来确定。本研究后，8名男孩和8名女孩将接受多巴胺拮抗剂甲氧氯普胺，以确定其解除青春期儿童LH脉冲频率和振幅日间抑制的能力。 这些研究将扩大我们对控制青春期时间和克里思的中枢神经系统通路的了解。

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.