MECHANISMS IN THE REGULATION OF PROLACTIN SECRETION

目前提案中概述的短期研究目标是 阐明个体(S)行为背后的细胞机制 催乳素分泌的调节剂(即多巴胺)。长期的研究 目标是为理解完整的 催乳素生理变化过程中的神经内分泌功能 分泌物。结合一种灌注技术测量颞叶 催乳素分泌模式及其成像测量技术 细胞内[Ca~(2+)]的变化，将使我们更深入地了解 刺激-分泌耦合。 催乳素是一种脑下垂体激素，参与许多生殖和 非生殖过程。与大多数内分泌细胞不同，内分泌细胞不 除非受到刺激，否则脑下垂体催乳素需要持续的分泌。 抑制，以保持其分泌活动在控制之下。初级阶段 抑制催乳素分泌的生理因素是多巴胺。然而， 多巴胺参与了与其他神经递质的复杂相互作用。 和荷尔蒙。这个系统的动态性和复杂性一直是 对我们理解催乳素控制的主要障碍。 因此，有必要界定每一项的行动机制。 在我们了解它们在体内的整合作用之前，我们还不能了解这些调控因子。 这些机制的阐明将通过应用 多种实验方法(免疫学、生物化学、 电生理学)以一致的方式以功能定义 分泌催乳素的细胞。分泌性和离子性的测量 单个乳酸菌的活动将提供对 它们的功能异质性，同时测量催乳素的释放 队列细胞群体将提供有关整合的、 它们的分泌行为的时间特征。 催乳素高分泌是不孕症的主要神经内分泌原因 在女人身上，在男人身上很重要。催乳素分泌肿瘤的缺陷 似乎是乳酸菌的先天异常，导致丢失 多巴胺能抑制。本文提出的研究将提供一种 用于检查细胞功能和所选方面的框架 与催乳素分泌的病理相关的异常。

The short-term research objective, as outlined in the current proposal, is to elucidate the cellular mechanisms underlying the action(s) of individual modulators (ie, dopamine) of prolactin secretion. The long-term research objective is to establish a basis for understanding integrated neuroendocrine function during physiological changes in prolactin secretion. Incorporation of a perfusion technique to measure temporal patterns of prolactin secretion and an imaging technique to measure intracellular [Ca2+], will yield greater insights into mechanisms of stimulus-secretion coupling. Prolactin is a pituitary hormone involved in numerous reproductive and nonreproductive processes. Unlike most endocrine cells, which do not secrete unless stimulated, the pituitary lactotrope requires constant inhibition to keep its secretory activity under control. The primary physiological inhibitor of prolactin secretion is dopamine. However, dopamine is involved in a complex interplay with other neurotransmitters and hormones. The dynamics and complexity of this system have been the major impediments to our understanding of the control of prolactin. Consequently, it is necessary to define the mechanisms of action of each of these regulators before we can understand their integrated actions in vivo. Elucidation of these mechanisms will be achieved through the application of diverse experimental approaches (immunology, biochemistry, electrophysiology) in a concerted manner to functionally-defined prolactin-secreting cells. Measurements of the secretory and ionic activity in single lactotropes will provide insights into the basis of their functional heterogeneity, while measurement of prolactin release from populations of cohort cells will provide information on the integrated, temporal profile of their secretory behavior. Prolactin hypersecretion is the major neuroendocrine cause of infertility in women and importance in men. The defect in prolactin-secreting tumors appears to be an intrinsic abnormality of the lactotropes, leading to loss of dopaminergic inhibition. The research proposed herein will provide a framework in which to examine selected aspects of cell function and abnormalities associated with pathologies of prolactin secretion.