Regulation of Prolactin Secretion at the Lactotroph

描述（由申请人提供）：本更新申请的中心假设是，在生理条件下，催乳素（PRL）的分泌被多巴胺（DA）抑制，催产素（OT）刺激，这些神经元的活动由下丘脑输入和PRL本身调节。我们将用一种新颖的跨学科实验和数学方法来检验这一假设，以达到以下具体目标：(1)确定DA、OT和PRL分泌之间生理相互作用的基础；(2)确定乳变性物对OT释放PRL特性的反应在发情周期阶段差异的生理基础；(3)确定OT对垂体乳变性物的作用机制；(4)确定DA和其他PRL释放调节剂对OT诱导乳变性物反应的关系。这些目标具有重要意义，因为它们将挑战公认的教条，即生理情况下PRL分泌仅受下丘脑DA的抑制控制。

DESCRIPTION (provided by applicant): The Central Hypothesis of this renewal application is that under physiological conditions, prolactin (PRL) secretion is inhibited by dopamine (DA) and stimulated by oxytocin (OT) and that the activities of these neurons are regulated by higher hypothalamic input and PRL itself. We will test this hypothesis with a novel interdisciplinary experimental and mathematical approach to the following specific aims: (1) To determine the basis for a physiological interaction between DA, OT and PRL secretion, (2) To determine the physiological basis for the estrous cycle stage differences in the response of lactotropes to the PRL-releasing properties of OT, (3) To characterize the mechanism of action of OT on pituitary lactotropes and (4) To characterize the relationship of DA and other modulators of PRL release on OT-induced responses in lactotropes. These aims are significant because they will challenge accepted dogma that PRL secretion in physiological circumstances is only under inhibitory control of hypothalamic DA. PUBLIC HEALTH RELEVANCE: Current clinical approaches to manipulating prolactin secretion involve manipulation of dopamine. For example, the benign hypersecreting pituitary tumor known as a prolactinoma is treated with the dopamine agonists bromocryptine or cabergoline. Each of these drugs has side effects which have serious implications for patients' welfare. Indeed, as our preliminary data suggest, if prolactin secretion is also under the control of peptidergic releasing factors such as oxytocin, then this may be another approach to treating disorders of prolactin secretion. Moreover, prolactin has been implicated in disorders related to more than 300 of its other biological actions. Results from these studies may serve as an approach to treating these disorders.