ON THE INVITRO AND INVIVO ACTIVITY OF A NEW SYNTHETIC HEXAPEPTIDE THAT ACTS ON THE PITUITARY TO SPECIFICALLY RELEASE GROWTH-HORMONE
ON THE INVITRO AND INVIVO ACTIVITY OF A NEW SYNTHETIC HEXAPEPTIDE THAT ACTS ON THE PITUITARY TO SPECIFICALLY RELEASE GROWTH-HORMONE
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DOI：
10.1210/endo-114-5-1537
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发表时间：
1984-01-01
期刊：
影响因子：
4.8
通讯作者：
HONG, A
中科院分区：
文献类型：
--
作者：
BOWERS, CY;MOMANY, FA;HONG, A
his - d - trp - ala - trp - d - ph - lys - nh2, [His1，Lys6]GHRP[生长激素释放肽]，是一种新的合成六肽，在体外和体内特异性地诱导GH[生长激素]的剂量相关释放，而不同时释放LH[黄体生成素]，FSH， TSH或PRL[催乳素]，在有限的体内研究中，胰岛素或胰高血糖素。这种小肽具有促垂体激素的特性。在体外垂体培养试验中，最小和最大活性剂量范围为1-10 ng/ml。它在老鼠、猴子、羊羔、小牛以及在特殊实验条件下的小鸡身上都很活跃，表明它没有物种依赖性。它在给老鼠静脉注射，皮下注射或静脉注射时都有活性。静脉注射后，生长激素水平在2分钟内升高，10-20分钟达到峰值，通常在2小时后恢复正常。由于这些肽对生长激素反应的时间过程不同，因此无法在大鼠单次注射s - c后直接比较[His1，Lys6]GHRP和GHRF-44、GHRF-40的效力。[His1，Lys6]GHRP的生长激素反应持续时间比这两种大肽都要长。SRIF[生长抑素]-14和SRIF-28均抑制生长激素对六肽的反应；然而，SRIF-28的体外活性是SRIF-14的4倍，体内活性是SRIF-14的7.5倍。当这种小肽每天1次或2次给予未成熟大鼠，持续9至25天，体重增加高于对照组。在体重增加研究结束时，垂体仍然对肽有充分的反应。[His1，Lys6]GHRP可能是一种有价值的肽，用于研究垂体生长激素的功能，此外，它有可能通过直接作用于垂体的部位诱导GH释放，从而增加各种正常动物的体重增加。
His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, [His1,Lys6]GHRP [growth hormone-releasing peptide], is a new synthetic hexapeptide which specifically elicits a dosage-related release of GH [growth hormone] in vitro and in vivo without a concomitant release of LH [luteinizing hormone], FSH, TSH or PRL [prolactin] and, in limited in vivo studies, insulin or glucagon. This small peptide has the attributes of a hypophysiotropic hormone. In vitro the minimum and maximum active dosages ranged from 1-10 ng/ml in the pituitary incubate assay. It was active in rats, monkeys, lambs, calves and under special experimental conditions, chicks, indicating its lack of species dependency. It was active when administered i.v., s.c. or i.p. to rats. After i.v. injection, GH levels rose within 2 min, peaked at +10-20 min, and by 2 h usually had returned to normal. It was not possible to directly compare the potencies of [His1,Lys6]GHRP and the GH-releasing factors GHRF-44 and GHRF-40 after a single s.c injection in rats because the time course of the GH response of these peptides was different. The GH response of [His1,Lys6]GHRP was longer in duration than either of these larger peptides. Both SRIF[somatostatin]-14 and SRIF-28 inhibited the GH response of the hexapeptide; however, SRIF-28 was about 4 times more active than SRIF-14 in vitro and 7.5 times more active in vivo. When this small peptide was administered s.c. once or twice daily to immature rats for 9 to 25 days, the body weight gain increased above the control. At the end of the weight gain studies the pituitary remained fully responsive to the peptide. [His1,Lys6]GHRP may be a valuable peptide for investigating the function of the pituitary somatotrophs and, in addition, it has the potential for increasing body weight gain of a variety of normal animals by inducing GH release via a direct pituitary site of action.