MECHANISMS OF HYPOTHALAMIC RELEASE OF SRIF AND GRF

以前的研究表明， 下丘脑中的肽能系统控制各种 垂体前叶激素 例如，已经表明， 生长激素释放因子（GRF）在下丘脑内起作用， 减少垂体前叶释放生长激素（GH）。 我们 研究表明，这种行为至少部分是由 促生长素抑制素（SRIF）释放的刺激。 GRF的作用， 刺激SRIF释放似乎通过β-内啡肽能介导 终端的冲击SRIF终端和刺激释放的 肽。 在本申请中，我们希望确定细胞内的 参与响应GRF释放SRIF的机制。 我们 假设SRIF可能刺激GRF释放，这可能是 参与其在下丘脑内发挥作用以刺激GH的能力 体内释放。 因此，赠款的另一个目的是确定 SRIF是否确实在体内和体外刺激GRF释放。 其他研究将关注其他递质在刺激神经元中的作用。 GRF和SRIF在体内和体外的释放。 这些研究应 增强我们对下丘脑控制GH释放的认识， 脑肽释放的一般机制是 控制。 它们可能在治疗内分泌疾病中具有临床意义。 或与GH分泌改变相关的代谢性疾病， 肢端肥大症、下丘脑-垂体GH缺乏、甲状腺功能减退、肥胖 和糖尿病

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.