REGULATION OF PROLACTIN SECRETION AT THE LACTOTROPH

垂体前叶催乳素（PRL）的分泌受下丘脑DA的紧张性抑制。 DA从三种解剖学上和功能上不同的下丘脑神经元群释放：（I）室周核的室周下丘脑多巴胺能（PHDA）神经元（A14），（II）结节垂体（THDA）和（III）弓状核的结节漏斗（TIDA）神经元（A12）。PHDA和THDA神经元分别终止于垂体的中间叶和神经叶。 THDA/PHDA终末释放的DA通过门脉短血管到达垂体前叶，TIDA神经元终止于正中隆起（ME）外带，通过门脉长血管向垂体前叶供应DA。 所有3个DA能神经内分泌神经元群体在白天表现出相似的活动节律性变化。 然而，它们对调节PRL分泌的相对贡献和重要性尚不清楚。 我们的中心假设是，所有3 DA能神经内分泌神经元群体的节律活动的节奏直接昼夜输入从视交叉上核，并有助于调节和调节PRL分泌。 本研究的目的有三：1）通过在恒定环境中进行体内实验，研究视交叉上直接输入对神经内分泌DA能活动的作用。 反义拮抗作用将用于验证SCN输入对神经内分泌DA能群体的功能意义。 2)研究PRL对DA能神经元昼夜节律的反馈作用。（3）探讨下丘脑DA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症。

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.