Regulation of prolactin secretion at the lactotroph

泌乳素细胞催乳素分泌的调节

• 批准号: 7990212
• 负责人: MARC Edward FREEMAN
• 金额: $ 1.62万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-03 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990212
• 关键词: Angiotensin II; Anterior; Anterior Pituitary Gland; Antisense Oligonucleotides; Antisense Technology; Back; Behavior; Blood; Calcitonin; Cell Nucleus; Characteristics; Circadian Rhythms; Data; Disease; Dopamine; Dopamine Receptor; Environment; Feeds; Figs - dietary; Fos-Related Antigens; Galanin; Genes; Hand; Health; Hormones; Hyperprolactinemia; Hypothalamic structure; Immediate-Early Genes; Incidence; Laboratories; Lactation; Lobe; Metabolism; Molecular; Nature; Neuraxis; Neurons; Neurosecretory Systems; Neurotensin; Oligonucleotides; Organism; Osmoregulation; Oxytocin; Peptides; Phenotype; Physiological; Pituitary Gland; Population; Progress Reports; Prolactin; Prolactin Receptor; Proteins; Rattus; Regulation; Reporting; Reproduction; Research Personnel; Role; Route; Staining method; Stains; Structure of nucleus infundibularis hypothalami; Substance P; System; Testing; Thyrotropin-Releasing Hormone; Time; Vasoactive Intestinal Peptide; Vasopressins; Work; dopaminergic neuron; immune function; lactotroph; magnocellular; malignant breast neoplasm; median eminence; neuropeptide Y; parvocellular; receptor; relating to nervous system; salsolinol; suprachiasmatic nucleus

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）：该应用的中心假设是，在生理条件下，垂体前叶的催乳素分泌受到多巴胺的抑制，并被催产素刺激，并且这些神经元的活性受到时钟基因的调节，较高的下丘脑输入和催乳素本身。这将通过追求4个具体目标来实现：（1）表征OT神经元在生理条件下控制PRL分泌中的作用。为此，将在生理诱导的PRL分泌期间表征大细胞和细胞细胞OT神经元的FOS或FRAS染色的发生率。 OT的拮抗剂将用于确定在生理情况下内源性OT是否控制PRL分泌。 （2）确定生理条件下OT和DA神经元活动传入的性质。这将通过首先确定OT神经元上是否有VIP受体来实现，然后对反义寡核苷酸进行VIP（请参阅进度报告和初步数据），并确定其对OT和DA神经元活动的影响，如FOS或FRAS染色所示。 （3）确定PRL是否以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，如果是这样，则将循环pRL免疫中和，或者施用卵子PRL并确定对这些神经元活性的影响。 （4）确定控制参与PRL分泌的神经内分泌DA神经元的昼夜节律的分子机制。首先要表征在恒定环境中在SCN，ARM或PEVN中表达它们的神经元的表达和神经元的表型。然后，使用反义技术，它们的破坏将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乳酸血症和乳腺癌相关的疾病的新方法。