NIL AND THE DYNAMIC RELEASE OF PRL

NIL 和 PRL 的动态释放

基本信息

批准号：
2144475
负责人：
L STEPHEN FRAWLEY
金额：
$ 19.36万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-01-01 至 1998-12-31
项目状态：
已结题

项目摘要

The neurointermediate lobe (NIL) of the rat adenohypophysis plays an essential role in regulating the dynamic release of prolactin (PRL) from the anterior pituitary (AP). This is evidenced by reports that surgical removal of the NIL blocks the acute release of PRL induced by two physiologically relevant stimuli-sucking and estrogen treatment. The NIL communicates with the AP via the short portal vessels, and chemical signals which convert the effects of evocative stimuli to changes in PRL cell function are probably delivered by this route. We have recently obtained compelling evidence that the NIL contributes two relevant activities to these processes. The first of these appears to be released by the suckling stimulus and renders mammotrophs more responsive to PRL- releasing agents. The other is induced by estrogen and acutely recruits additional PRL-releasing cells into the secretory population. Interestingly, both the responsiveness and recruitment activities can be mimicked in vitro by the di-acetylated variant of alpha-melanocyte stimulating hormone (MSH) secreted by the rat NIL. Accordingly, our overall goal is to elucidate how the NIL, through the mediation of this peptide, plays a requisite role in the dynamic release of PRL. In pursuit of this objective, we will test the hypotheses that: 1) acetylated alpha-MSH contribution to suckling-induced PRL release; and 2) acetylated alpha-MSH released from the NIL also mediates estrogen- induced PRL release by recruitment of additional mammotrophs. We plan to take a multificated approach to these problems. Reverse hemolytic plaque assays will be employed to analyze hormone secretin at the single cell level. Molecular strategies will provide complementary information on gene expression. In addition, several in vivo studies are planned to confirm the biological relevance of our in vitro findings. Thus, by integrating information derived from studies at multiple levels of organizational complexity-cellular, molecular, and organismal-we intend to gain a comprehensive understanding about the neuroendocrine mechanisms that govern the dynamic release of PRL. Such information is essential for identifying the causes of, and developing treatments for, pathologies of PRL release in humans.

大鼠腺垂体的神经中间叶（NIL）起着在调节催乳素（PRL）的动态释放中发挥着重要作用垂体前叶（AP）。有报告证明了这一点，即外科手术去除 NIL 可阻止两种物质诱导的 PRL 急性释放生理相关的刺激吸吮和雌激素治疗。零通过短门脉血管和化学物质与 AP 进行通信将唤起刺激的效果转化为 PRL 变化的信号细胞功能可能是通过这条途径传递的。我们最近有获得了令人信服的证据，证明 NIL 贡献了两个相关的这些过程的活动。其中第一个似乎已发布通过哺乳刺激，使乳腺营养细胞对 PRL 更敏感脱模剂。另一种是由雌激素诱导并急剧招募额外的释放 PRL 的细胞进入分泌群体。有趣的是，响应能力和招聘活动都可以通过α-黑素细胞的二乙酰化变体在体外模拟大鼠 NIL 分泌的刺激激素 (MSH)。因此，我们的总体目标是阐明 NIL 如何通过这种调解肽，在 PRL 的动态释放中起着必要的作用。在为了实现这一目标，我们将检验以下假设：1) 乙酰化 α-MSH 对哺乳诱导的 PRL 释放的贡献；和 2) NIL 释放的乙酰化 α-MSH 也介导雌激素- 通过募集额外的促乳腺激素诱导 PRL 释放。我们计划采取多种方法解决这些问题。逆溶血噬菌斑测定将用于分析单次激素分泌素细胞水平。分子策略将提供补充信息关于基因表达。此外，还计划进行几项体内研究确认我们的体外研究结果的生物学相关性。因此，通过整合从多个层面的研究中获得的信息组织复杂性——细胞、分子和有机体——我们打算全面了解神经内分泌机制控制 PRL 的动态释放。这些信息是必不可少的用于确定病理的原因并开发治疗方法人类 PRL 释放量。