Regulation of prolactin secretion at the lactotroph

泌乳素细胞催乳素分泌的调节

• 批准号: 7017086
• 负责人: MARC Edward FREEMAN
• 金额: $ 29.84万
• 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 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017086
• 关键词: antisense nucleic acid; biological signal transduction; circadian rhythms; confocal scanning microscopy; dopamine; dopamine receptor; hormone inhibitor; hormone regulation /control mechanism; hypothalamus; immunocytochemistry; laboratory rat; neurons; oxytocin; phosphorylation; pituitary gland; polymerase chain reaction; prolactin; radioimmunoassay; secretion; suprachiasmatic nucleus; vasoactive intestinal peptide

DESCRIPTION (provided by applicant): The central hypothesis of this application is that under physiological conditions, prolactin secretion from the anterior lobe of the pituitary gland is inhibited by dopamine and stimulated by oxytocin and that the activities of these neurons are regulated by clock genes, higher hypothalamic input and prolactin itself. This will be accomplished by pursuing 4 specific aims: (1) To characterize the role of OT neurons in control of PRL secretion under physiological conditions. To accomplish this, the incidence of FOS or FRAs staining of magnocellular and parvocellular OT neurons will be characterized during periods of physiologically induced PRL secretion. Antagonists of OT will be used to determine if endogenous OT controls PRL secretion under physiological circumstances. (2) To determine the nature of the afferent control of OT and DA neuronal activities under physiological conditions. This will be accomplished by first determining if there are VIP receptors on OT neurons and then administer antisense oligonucleotides to VIP (see Progress Report and Preliminary Data) and determine their effects on OT and DA neuronal activity as indicated by FOS or FRAs staining. (3) To determine if PRL feeds back on either OT neurons and/or their afferent controls to regulate their activities. First, it will be determined if OT neurons have PRL receptors and if so, immunoneutralize circulating PRL or administer ovine PRL and determine the effect on activity of these neurons. (4) To determine the molecular mechanisms controlling the circadian rhythm of neuroendocrine DA neurons involved in PRL secretion. The expression of clock genes and the phenotype of the neurons expressing them in the SCN, ARM or PeVN in a constant environment will first be characterized. Then, using antisense technology, their disruption will show function of the expressing neurons. The health relatedness of this project is to suggest new ways of treating diseases related to hyperprolactinemia and breast cancer.

描述（由申请人提供）：本申请的中心假设是，在生理条件下，垂体前叶的催乳素分泌受多巴胺抑制并受催产素刺激，这些神经元的活动受时钟基因、更高的下丘脑输入和催乳素本身调节。这将通过追求4个具体目标来实现：（1）表征生理条件下OT神经元在控制PRL分泌中的作用。为了实现这一点，将在生理诱导的PRL分泌期间表征大细胞和小细胞OT神经元的FOS或FRA染色的发生率。OT的拮抗剂将用于确定内源性OT是否控制生理环境下的PRL分泌。(2)确定在生理条件下OT和DA神经元活动的传入控制的性质。这将通过首先确定OT神经元上是否存在VIP受体来实现，然后对VIP施用反义寡核苷酸（参见进展报告和初步数据）并确定它们对OT和DA神经元活性的影响，如FOS或FRA染色所示。(3)确定PRL是否反馈OT神经元和/或其传入控制以调节其活动。首先，将确定OT神经元是否具有PRL受体，如果是，则免疫中和循环PRL或施用绵羊PRL并确定对这些神经元活性的影响。(4)目的：探讨参与PRL分泌的神经内分泌DA神经元昼夜节律的分子机制。首先将表征在恒定环境中SCN、ARM或PeVN中时钟基因的表达和表达它们的神经元的表型。然后利用反义技术将其破坏，以显示表达神经元的功能。该项目的健康相关性是提出治疗与高催乳素血症和乳腺癌有关的疾病的新方法。