Regulation of Prolactin Secretion at the Lactotroph

催乳素分泌的调节

• 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
• 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

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（由申请人提供）：这种更新应用的中心假设是，在生理条件下，多巴胺（DA）抑制催乳素（PRL）分泌，并被催产素（OT）刺激，并且这些神经元的活性受到较高的下丘脑输入和PRL本身的调节。我们将通过一种新型的跨学科实验和数学方法来检验以下特定目的：（1）确定DA，OT和PRL分泌之间的生理相互作用的基础，（2）确定偏发周期阶段差异在lactotropes响应中对lactopers响应的生理基础差异，而在PRL-REALEAS上的依赖机制（3）表征（3）表征（3）表征依赖于（3）的特征范围（3）构成效果的作用。乳酸和（4）表征DA和PRL释放的其他调节剂在乳糖中的OT诱导反应上的关系。这些目标很重要，因为它们会挑战公认的教条，即在生理环境中的PRL分泌仅在下丘脑DA的抑制作用下。 公共卫生相关性：当前操纵催乳素分泌的临床方法涉及多巴胺的操纵。例如，用多巴胺激动剂溴烯普汀或cabergoline治疗称为催乳素瘤的良性高血压垂体肿瘤。这些药物中的每一个都有副作用，对患者的福利具有严重影响。确实，正如我们的初步数据所表明的那样，如果催乳素分泌也受肽释放因子（例如催产素）的控制，那么这可能是治疗催乳素分泌疾病的另一种方法。此外，催乳素已与与300多种其他生物学作用有关的疾病牵涉。这些研究的结果可能是治疗这些疾病的方法。