MECHANISMS IN THE REGULATION OF PROLACTIN SECRETION

目前建议中概述的短期研究目标是 阐明个体作用的细胞机制， 催乳素分泌的调节剂（即多巴胺）。 长期研究 目标是建立一个基础，了解综合 催乳素生理变化过程中的神经内分泌功能 分泌物 结合灌注技术测量时间 催乳素分泌的模式和一种成像技术来测量 细胞内[Ca 2 +]，将产生更深入的了解机制， 刺激-分泌偶联 催乳素是一种垂体激素，参与许多生殖和 非生殖过程。 不像大多数内分泌细胞， 除非受到刺激，否则垂体催乳素需要恒定的 抑制以保持其分泌活性在控制之下。 主 催乳素分泌的生理抑制剂是多巴胺。 然而，在这方面， 多巴胺与其他神经递质有着复杂的相互作用 和荷尔蒙。 这个系统的动态和复杂性一直是 这是我们理解催乳素控制的主要障碍。 因此，有必要确定每种药物的作用机制， 在我们了解它们在体内的综合作用之前， 这些机制的阐明将通过应用 不同的实验方法（免疫学，生物化学， 电生理学）以协调一致的方式 催乳素分泌细胞 分泌和离子测量 活性在单一的催乳素将提供洞察的基础上， 他们的功能异质性，而催乳素释放的测量， 群组细胞群将提供关于整合的， 其分泌行为的时间曲线。 催乳素分泌过多是不孕症的主要神经内分泌原因 在女性和男性的重要性。 泌乳素分泌肿瘤的缺陷 似乎是一种内在的异常的催乳素，导致损失 多巴胺能抑制 本文提出的研究将提供一个 框架，在其中检查细胞功能的选定方面， 与催乳素分泌病理学相关的异常。

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.