Lengyel A-M J
Divisão de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2006 Aug;39(8):1003-11. doi: 10.1590/s0100-879x2006000800002.
Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a) discovery of this peptide, b) mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c) regulation of growth hormone release in man after intravenous administration of these peptides.
生长激素的分泌传统上受两种下丘脑激素调节，即生长激素释放激素和生长抑素。在过去十年中提出了第三条途径，涉及生长激素促分泌素。胃泌素是一种新型酰化肽，主要由胃产生。它也在下丘脑中合成，并存在于其他几种组织中。这种内源性生长激素促分泌素是通过反向药理学发现的，当时最初生产了一组合成生长激素释放化合物，导致分离出一种孤儿受体，最终分离出其内源性配体。胃泌素与活性受体结合以增加生长激素释放和食物摄入量。目前尚不清楚下丘脑和循环中的胃泌素如何参与生长激素释放的控制。内源性胃泌素可能起到放大生长激素分泌的基本模式的作用，优化促生长激素细胞对生长激素释放激素的反应性。它可能在促生长激素细胞中激活多个相互依赖的细胞内途径，涉及蛋白激酶C、蛋白激酶A和细胞外钙系统。然而，由于胃泌素在体内具有更大的释放生长激素的能力，其主要作用部位是下丘脑。在本综述中，我们总结了关于以下方面的现有数据：a）这种肽的发现，b）生长激素促分泌素和胃泌素的作用机制以及对生长激素调节的可能生理作用，c）静脉注射这些肽后人体生长激素释放的调节。
