Bowers C Y, Momany F A, Reynolds G A, Hong A
Endocrinology. 1984 May;114(5):1537-45. doi: 10.1210/endo-114-5-1537.
His-DTrp-Ala-Trp-DPhe-LysNH2, [His1,Lys6] GHRP, is a new synthetic hexapeptide which specifically elicits a dosage-related release of GH in vitro and in vivo without a concomitant release of LH, FSH, TSH, or PRL and, in limited in vivo studies, insulin or glucagon. Our results indicate that 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 iv, sc, or ip to rats. After iv 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 sc 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-14 and SRIF-28 inhibited the GH response of the hexapeptide; however, SRIF-28 was about four times more active than SRIF-14 in vitro and 7.5 times more active in vivo. When this small peptide was administered sc once or twice daily to immature rats for 9 or 25 days, the BW gain increased above the control. At the end of the weight gain studies the pituitary remained fully responsive to the peptide. Thus, [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 BW gain of a variety of normal animals by inducing GH release via a direct pituitary site of action.
组氨酸 - 色氨酸 - 丙氨酸 - 色氨酸 - 二苯丙氨酸 - 赖氨酸氨基，即[His1,Lys6]生长激素释放肽（GHRP），是一种新型合成六肽，它在体外和体内能特异性引发与剂量相关的生长激素释放，同时不会伴随促黄体生成素（LH）、促卵泡生成素（FSH）、促甲状腺激素（TSH）或催乳素（PRL）的释放，并且在有限的体内研究中，也不会引发胰岛素或胰高血糖素的释放。我们的研究结果表明，这种小肽具有促垂体激素的特性。在垂体孵育试验中，体外最小和最大活性剂量范围为1 - 10纳克/毫升。它在大鼠、猴子、羔羊、小牛以及在特殊实验条件下的雏鸡中均有活性，表明其不依赖物种。给大鼠静脉注射、皮下注射或腹腔注射时它都有活性。静脉注射后，生长激素水平在2分钟内升高，在10 - 20分钟达到峰值，到2小时通常恢复正常。在大鼠单次皮下注射后，无法直接比较[His1,Lys6]GHRP与生长激素释放因子GHRF - 44和GHRF - 40的效力，因为这些肽的生长激素反应时间进程不同。[His1,Lys6]GHRP的生长激素反应持续时间比这两种较大的肽都长。促甲状腺激素释放抑制因子（SRIF）- 14和SRIF - 28均抑制该六肽的生长激素反应；然而，SRIF - 28在体外的活性约为SRIF - 14的四倍，在体内则为其7.5倍。当这种小肽每天给未成熟大鼠皮下注射一次或两次，持续9天或25天时，体重增加超过对照组。在体重增加研究结束时，垂体对该肽仍保持完全反应性。因此，[His1,Lys6]GHRP可能是一种用于研究垂体生长激素细胞功能的有价值的肽，此外，它有可能通过直接作用于垂体部位诱导生长激素释放，从而增加多种正常动物的体重增加。
