Katakami H, Matsukura S
Third Department of Medicine, Miyazaki Medical College.
Nihon Naibunpi Gakkai Zasshi. 1992 Oct 20;68(10):1057-72. doi: 10.1507/endocrine1927.68.10_1057.
Growth hormone (GH)-releasing hormone (GRH) is a stimulatory hypothalamic hypophysiotropic hormone which, along with an inhibitory peptide, somatostatin (SRIF), regulates the synthesis and secretion of GH in anterior pituitary somatotrophs. Although GHRH genes in several species have been characterized, there is only a limited understanding of the neural and hormonal mechanisms regulating GRH biosynthesis and secretion. Recent progress in PCR and in situ hybridization techniques as well as hGRF-transgenic animal models have provided an opportunity to study the regulation of GRH gene expression and secretion as well as its metabolism. The difference in 5'-untranslated sequences in both mouse and rat GRH cDNAs from hypothalamus and placenta has also suggested tissue-specific regulation of the GRH gene. GH excess has been shown to result in a decrease in hypothalamic GRH mRNA as well as GRH content and secretion while GH deficiency caused by hypophysectomy, hypothyroidism or genetic dwarfism causes an increase in GRH mRNA levels as tested by Northern blot analysis or in situ hybridization. Treatment of animals with GH or SRIF inhibits the increased GRH gene expression in the hypothalamic arcuate nucleus. Double immunocytochemistry for hypothalamic GRH and SRIF has shown both axo-perikaryal and axo-axonal connections between GRH- and SRIF- containing neurons. SRIF binding and GH receptor mRNA are demonstrated on a subpopulation of GRH-containing neurons in the hypothalamic arcuate nucleus. It is therefore possible to conclude that regulation of GRH gene expression, primarily related to inhibitory feedback effects of GH and IGFs on hypothalamic GRH gene expression, is mediated at least in part by SRIF or GH. The single transcript of the human GRH gene encodes a 108 amino acid precursor, prepro-hGRH, which is cleaved into the signal peptide and the remaining peptide, pro-hGRH. The latter is further processed to yield two equipotent forms of the releasing hormone, hGRH(1-44)-NH2, hGRH(1-40)-OH, and a carboxyl-terminal peptide (hGCTP) of unknown function. Studies in transgenic mice demonstrate the processing of hGRH-prohormone into both mature forms of hGRH and hGCTP, and provide evidence that hGRH(1-40)-OH is derived from hGRH(1-44)-NH2.(ABSTRACT TRUNCATED AT 400 WORDS)
生长激素（GH）释放激素（GRH）是一种刺激性的下丘脑促垂体激素，它与一种抑制性肽——生长抑素（SRIF）一起，调节垂体前叶生长激素细胞中GH的合成与分泌。尽管已经对几种物种的GHRH基因进行了表征，但对调节GRH生物合成和分泌的神经及激素机制的了解仍然有限。聚合酶链反应（PCR）、原位杂交技术以及hGRF转基因动物模型方面的最新进展，为研究GRH基因表达、分泌及其代谢的调节提供了契机。小鼠和大鼠下丘脑及胎盘GRH cDNA中5'-非翻译序列的差异，也提示了GRH基因的组织特异性调节。研究表明，GH过量会导致下丘脑GRH mRNA以及GRH含量和分泌减少，而垂体切除、甲状腺功能减退或遗传性侏儒症所致的GH缺乏，则会使GRH mRNA水平升高，这通过Northern印迹分析或原位杂交得以证实。用GH或SRIF处理动物，可抑制下丘脑弓状核中GRH基因表达的增加。下丘脑GRH和SRIF的双重免疫细胞化学显示，含GRH和含SRIF的神经元之间存在轴突-胞体连接和轴突-轴突连接。在下丘脑弓状核中，GRH神经元亚群上可检测到SRIF结合及GH受体mRNA。因此，可以得出结论，GRH基因表达的调节主要与GH和胰岛素样生长因子（IGF）对下丘脑GRH基因表达的抑制性反馈作用有关，至少部分是由SRIF或GH介导的。人类GRH基因的单一转录本编码一种108个氨基酸的前体，即前激素原hGRH，它被切割成信号肽和剩余的肽，即激素原hGRH。后者进一步加工产生两种等效形式的释放激素，即hGRH(1-44)-NH2、hGRH(1-40)-OH，以及一种功能未知的羧基末端肽（hGCTP）。对转基因小鼠的研究表明，hGRH前激素可加工成两种成熟形式的hGRH和hGCTP，并提供了证据表明hGRH(1-40)-OH源自hGRH(1-44)-NH2。（摘要截取自400词）
