Regulation of Prolactin Secretion at the Lactotroph

催乳素分泌的调节

基本信息

批准号：
8055775
负责人：
Richard Bertram
金额：
$ 1.5万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-05-01 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8055775
关键词：
Address Adverse effects Affect Angiotensin II Anterior Pituitary Gland Behavior Benign Biological Blood Bromocriptine Calcitonin Calcium Calcium Signaling Cell Nucleus Cells Clinical Coupled Data Disease Dopamine Dopamine Agonists Dopamine Receptor Endothelin Environment Estrous Cycle Experimental Designs Figs - dietary GTP-Binding Proteins Galanin Hormones Hypothalamic structure Implant Lactation Metabolism Modeling Nature Neurohormones Neurons Neurosecretory Systems Neurotensin Oligonucleotides Organism Osmoregulation Ovarian Oxytocin Pathway interactions Patients Pharmaceutical Preparations Physiological Pituitary Gland Pituitary Neoplasms Population Progress Reports Prolactin Prolactin Release-Inhibiting Hormone Prolactin-Releasing Hormone Prolactinoma Property Rattus Regulation Reporting Reproduction Role Self-control as a personality trait Signal Pathway Signal Transduction Site Social Welfare Staging Steroids Stimulus Structure of nucleus infundibularis hypothalami Substance P Testing Thyrotropin-Releasing Hormone Time Vasoactive Intestinal Peptide Vasopressins base cabergoline desensitization design dopaminergic neuron immune function inhibitor/antagonist insight interdisciplinary approach lactotroph mathematical model model development neuropeptide Y novel prevent public health relevance relating to nervous system release factor research study response suprachiasmatic nucleus

项目摘要

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.

描述（申请人提供）：本次更新申请的中心假设是，在生理条件下，催乳素（PRL）的分泌受到多巴胺（DA）的抑制，并受到催产素（OT）的刺激，并且这些神经元的活动受到更高水平的调节。下丘脑输入和 PRL 本身。我们将采用新颖的跨学科实验和数学方法来检验这一假设，以实现以下具体目标：(1) 确定 DA、OT 和 PRL 分泌之间生理相互作用的基础，(2) 确定动情周期的生理基础催乳素对 OT 的 PRL 释放特性的反应的阶段差异，(3) 表征 OT 对垂体催乳素的作用机制，(4) 表征 DA 和其他催乳素调节剂的关系泌乳素中 OT 诱导反应的 PRL 释放。这些目标意义重大，因为它们将挑战公认的教条，即生理环境下 PRL 的分泌仅受下丘脑 DA 的抑制控制。公共卫生相关性：目前控制催乳素分泌的临床方法涉及多巴胺的控制。例如，良性分泌过多的垂体肿瘤（称为催乳素瘤）可以用多巴胺激动剂溴隐亭或卡麦角林治疗。这些药物中的每一种都有副作用，对患者的福利有严重影响。事实上，正如我们的初步数据表明的那样，如果催乳素分泌也受到肽能释放因子（例如催产素）的控制，那么这可能是治疗催乳素分泌障碍的另一种方法。此外，催乳素与 300 多种其他生物作用相关的疾病有关。这些研究的结果可以作为治疗这些疾病的方法。