MECHANISMS OF HYPOTHALAMIC RELEASE OF SRIF AND GRF

以前的研究已经表明，在 控制下丘脑释放各种多肽的肽能系统 脑下垂体前叶激素。例如，已经表明， 生长激素释放因子(GRF)在下丘脑内作用于 减少垂体前叶释放生长激素(GH)。我们的 研究表明，这一行动至少在一定程度上是由 刺激生长抑素(SRIF)的释放。GRF的作用 刺激SRIF释放似乎是通过β-内啡肽能介导的 冲击SRIF端子并刺激释放的端子 多肽。在此应用程序中，我们希望确定细胞内 SRIF的释放参与了对GRF的反应。我们 假设SRIF可以刺激GRF的释放，这可能是 参与其在下丘脑内刺激生长激素的能力 在体内释放。因此，赠款的另一个目的将是确定 SRIF是否真的在体内和体外刺激GRF的释放。 其他研究将涉及其他递质在刺激中的作用 体内和体外释放GRF和SRIF。这些研究应该 增强我们对下丘脑控制GH释放的知识，并 脑肽释放的一般机制是什么？ 控制住了。它们在内分泌治疗中可能具有临床意义。 或与生长激素分泌改变相关的代谢性疾病，如 肢端肥大症、下丘脑-垂体生长激素缺乏症、甲状腺功能减退、肥胖 还有糖尿病。

Previous studies have indicated that there are interactions amongst peptidergic systems in the hypothalamus to control the release of various anterior pituitary hormones. For example, it has already been shown that growth hormone releasing factor (GRF) acts within the hypothalamus to reduce the release of growth hormone (GH)- by the anterior pituitary. Our studies have shown that this action is at least in part brought about by a stimulation of somatostatin (SRIF) release. The action of GRF to stimulate SRIF release appears to be mediated via beta-endorphinergic terminals which impinge on the SRIF terminals and stimulate the release of the peptide. In this application we wish to determine the intracellular mechanisms involved in the release of SRIF in response to GRF. We hypothesize that SRIF may stimulate release of GRF and that this may be involved in its ability to act within the hypothalamus to stimulate GH release in vivo. Therefore, another aim of the grant will be to determine whether indeed SRIF stimulates GRF release both in vivo and in vitro. Other studies will concern the role of other transmitters in stimulating the release of GRF and SRIF in vivo and in vitro. These studies should enhance our knowledge of the hypothalamic control of GH release and also of the general mechanisms by which the release of brain peptides is controlled. They may have clinical relevance in the treatment of endocrine or metabolic diseases associated with altered GH secretion such as acromegaly, hypothalamic-pituitary GH deficiency, hypothyroidism, obesity and diabetes.