REGULATION OF PROLACTIN SECRETION AT THE LACTOTROPH

垂体前叶泌乳素（PRL）的分泌受到来自下丘脑的DA的强直性抑制。DA从三个解剖和功能上不同的下丘脑神经元群释放：(I)脑室周围核的下丘脑多巴胺能（PHDA）神经元（A14）， （II）垂体结节（THDA）和（III）弓状核的垂体结节（TIDA）神经元（A12）。PHDA和THDA神经元分别终止于脑垂体的中间叶和神经叶。DA由THDA/PHDA终端释放，经短门静脉到达前叶，而TIDA神经元终端于中突外区（ME），经长门静脉向垂体前叶供应DA。所有3种能性神经内分泌神经元群在白天的活动中表现出相似的节律变化。然而，它们在调节PRL分泌中的相对贡献和重要性尚不清楚。我们的中心假设是，所有3种DAergic神经内分泌神经元群的节律性活动由视交叉上核的直接昼夜节律输入来调节，并参与PRL分泌的调节，并受PRL分泌的调节。本文将探讨三个具体目标：1)通过在恒定环境下进行体内实验，表征视交叉上直接输入对神经内分泌能活动的作用。反义拮抗将用于验证SCN输入对神经内分泌能人群的功能意义。2)表征PRL在神经内分泌能神经元日常活动中的反馈作用；(3)明确下丘脑神经内分泌能神经元昼夜节律调节的信号转导机制。这些研究的结果导致更好地了解PRL分泌的控制，从而治疗与高催乳素血症相关的不孕状态。

The secretion of prolactin (PRL) from the anterior pituitary gland is under tonic inhibition by DA of hypothalamic origin. DA is released from three anatomically and functionally distinct hypothalamic neuronal populations: (I) periventricular hypothalamic dopaminergic (PHDA) neurons of the periventricular nucleus (A14), (II) tuberohypophysial (THDA) and (III) tuberoinfundibular (TIDA) neurons of the arcuate nucleus (A12). PHDA and THDA neurons terminate in the intermediate and neural lobes of the pituitary gland, respectively. DA, released from THDA/PHDA terminal reaches the anterior lobe through the short portal vessels, while TIDA neurons terminate in the external zone of the median eminence (ME) and supply the anterior pituitary gland with DA through the long portal vessels. All 3 DAergic neuroendocrine neuron populations exhibit similar rhythmic changes in activity during the day. However, their relative contribution and importance to the regulation of PRL secretion is not understood. Our central hypothesis is that the rhythmic activity of all 3 DAergic neuroendocrine neuron populations are paced by direct circadian input from the suprachiasmatic nucleus and contribute to the regulation of and are regulated by PRL secretion. Three specific aims will be attacked: 1) To characterize the role of the direct suprachiasmatic input to neuroendocrine DAergic activity by conducting in vivo experiments in constant environments. Antisense antagonism will be used to verify the functional significance of the SCN input to the neuroendocrine DAergic population. 2) To characterize the feedback role of PRL in the daily activity of neuroendocrine DAergic neurons and (3) To identify the signal transduction mechanisms involved in the circadian regulation of hypothalamic neuroendocrine DAergic neurons. Results of these studies lead to a better understanding of the control of PRL secretion and hence treatment of states of infertility associated with hyperprolactinemia.