MECHANISMS IN THE REGULATION OF PROLACTIN SECRETION

哺乳动物垂体前叶催乳素的分泌 受到各种激素的持续修饰， 神经传递素 这些调节剂，反过来，经常表现出 多个动作和/或对多个细胞类型的动作。 研究 催乳素调节的存在进一步复杂化， 催乳素分泌细胞的亚群可能表现出 对各种调节剂的反应性差异。 的 这些调节剂对催乳素的联合或顺序作用 解放是不太了解的。 此外，研究评估 这些因素的个别影响主要利用了 垂体组织或细胞制剂，而不考虑 催乳素功能的异质性。 因此， 关于假定催乳素生理作用的结论 监管机构仍然难以捉摸。 为了了解催乳素分泌的调节器是如何工作的 首先必须明确它们各自是如何相互协调。 在 此外，催乳素分泌者亚群的鉴定 受这些监管机构的不同影响是固有的， 认识 该提案概述了多学科 多巴胺作用机制的实验研究 抑制催乳素从单个催乳素细胞释放 分离自正常大鼠垂体前叶组织。 可行 泌乳素分泌细胞将使用 基于免疫学反向溶血空斑测定。 泌乳素 分泌物将根据1）多少催乳素 它们释放（大斑块与小斑块形成者），或2） 它们是只释放催乳素还是同时释放催乳素和 生长激素. 这些细胞将用于研究细胞 和细胞膜对多巴胺的反应 钳位技术 这项技术的多功能性将使 评估细胞内信使系统的作用，以及 作为多巴胺介导的膜离子机制， 对催乳素释放的作用。 的作用机制的表征 个别调制器将建立必要的基础， 了解神经内分泌的综合功能， 催乳素分泌的生理变化。 另外这款 研究将提供一个框架，在其中检查细胞 以及与之相关的膜特性和异常 激素分泌的病理学。 因此，这些研究具有 直接影响生育力和生殖的调节， 高催乳素血症的临床治疗。

Secretion of prolactin in the mammalian anterior pituitary gland is subject to continual modification by a variety of hormones and neurotransmitters. These modulators, in turn, often demonstrate multiple actions and/or actions on multiple cell types. The study of prolactin regulation is further complicated by the existence of subpopulations of prolactin-secreting cells which may exhibit differences in responsiveness to various modulators. The combined or sequential effects of these modulators on prolactin release are poorly understood. Furthermore, studies evaluating the individual effects of these factors have primarily utilized pituitary tissue or cell preparations without taking into account the functional heterogeneity among lactotrophs. Thus, definitive conclusions regarding the physiological roles of putative prolactin regulators remain elusive. In order to understand how regulators of prolactin secretion work in concert, it is first necessary to define how they individually. In addition, identification of subpopulations of prolactin secretors differentially affected by these regulators is inherent to this understanding. This proposal outlines a multidisciplinary experimental approach to the study of mechanism(s) of dopamine inhibition of prolactin release from individual lactotrophs dissociated from normal rat anterior pituitary tissue. Viable prolactin-secreting cells will be identified using the immunologically-based reverse hemolytic plaque assay. Prolactin secretors will be subgrouped according to 1) how much prolactin they release (large plaque- vs. small plaque-formers), OR 2) whether they release only prolactin or release both prolactin and growth hormone. These cells will then be used to study cellular and membrane responses to dopamine using the gigaseal patch clamp technique. The versatility of this technique will enable evaluation of the roles of intracellular messenger systems as well as membrane ionic mechanisms in the mediation of dopamine's action(s) on prolactin release. Characterization of the mechanisms underlying the action of individual modulators will establish the necessary basis for understanding integrated neuroendocrine function during physiological changes in prolactin secretion. In addition, this research will provide a framework in which to examine cellular and membrane properties and abnormalities associated with pathologies of hormone secretion. As such, these studies have a direct bearing on the regulation of fertility and reproduction and in the clinical management of hyperprolactinemia.