Tiulpakov A N, Brook C G, Pringle P J, Peterkova V A, Volevodz N N, Bowers C Y
Paediatric Unit, National Endocrinological Research Centre, Moscow, Russia.
Clin Endocrinol (Oxf). 1995 Sep;43(3):347-50. doi: 10.1111/j.1365-2265.1995.tb02042.x.
Synthetic growth hormone releasing peptides (GHRP) have potent GH-releasing activity in vivo and in vitro. The nature of the interaction of GHRP and naturally occurring GH releasing hormone (GHRH) is still far from clear. We investigated GH release in response to individual peptide doses or combined doses of GHRH1-29NH2 and GHRP-2, a novel GH-releasing peptide, in normal adults.
Subjects underwent three tests in a randomized order: (1) i.v. bolus of GHRH1-29NH2 (1 microgram/kg BW), (2) i.v. bolus of GHRP-2 (1 microgram/kg BW), (3) i.v. bolus of GHRH1-29NH2 combined with GHRP-2 (same dosages).
Eight healthy non-obese male volunteers, aged 25-34 years.
Serum GH concentrations were measured by IRMA at -15, 0, +10, 20, 30, 45, 60, 75, 90 and 120 minutes after the boluses.
Peak GH levels in response to GHRH1-29NH2, GHRP-2 and the combined GHRH1-29NH2 and GHRP-2 administrations were observed between 20 and 45 minutes. Peak GH levels at 30 minutes were 32.8 +/- 27.3 (mean +/- SD), 109.7 +/- 56.1 and 140.9 +/- 80.6 mU/l, respectively. The area under the curve for GH levels (GH AUC) calculated for the first 90 minutes after the GHRH1-29NH2 test (2061.2 +/- 1601.9 mU/lmin) was significantly lower than those after GHRP-2 (6205.1 +/- 3216.9 mU/lmin) and the combined GHRH1-29NH2 and GHRP-2 challenge (9788.3 +/- 5530.4 mU/lmin) (P = 0.0003 and P = 0.00005, respectively; paired Student's t-test for log transformed data). Although the GH AUC of the GHRP-2 test and the combined GHRH1-29NH2 and GHRP-2 test differed significantly (P = 0.016, t-test), the latter was not significantly different from the sum of the GH AUCs of each subject after the separate tests.
Although the GH releasing potency of GHRP-2 significantly exceeded that of GHRH1-29NH2, we were not able to demonstrate synergy between the two substances. It is possible that GHRP-2 given in our study GHRP-2 significantly exceeded that of GHRH1-29NH2, we were not able to demonstrate synergy between the two substances. It is possible that GHRP-2 given in our study in higher molar quantities than GHRH1-29NH2 masked the effect of the latter.
合成生长激素释放肽(GHRP)在体内和体外均具有强大的生长激素释放活性。GHRP与天然存在的生长激素释放激素(GHRH)相互作用的本质仍远未明确。我们研究了正常成年人对GHRH1 - 29NH2和一种新型生长激素释放肽GHRP - 2的单独肽剂量或联合剂量的生长激素释放反应。
受试者按随机顺序接受三项测试:(1)静脉推注GHRH1 - 29NH2(1微克/千克体重),(2)静脉推注GHRP - 2(1微克/千克体重),(3)静脉推注GHRH1 - 29NH2与GHRP - 2联合使用(相同剂量)。
8名健康非肥胖男性志愿者,年龄在25 - 34岁之间。
推注后-15、0、+10、20、30、45、60、75、90和120分钟时通过免疫放射分析(IRMA)测量血清生长激素浓度。
在20至45分钟之间观察到对GHRH1 - 29NH2、GHRP - 2以及联合给予GHRHl - 29NH2和GHRP - 2后的生长激素峰值水平。30分钟时的生长激素峰值水平分别为32.8±27 .3(平均值±标准差)、109.7±56.1和140.9±80.6 mU/l。GHRH1 - 29NH2测试后前90分钟计算的生长激素水平曲线下面积(生长激素AUC)(2061.2±1601.9 mU/l·min)显著低于GHRP - (6205.1±3216.9 mU/l·min)以及联合给予GHRH1 - 29NH2和GHRP - 2激发后的水平(9788.3±5530.4 mU/l·min)(分别为P = 0.0003和P = 0.00005;对对数转换数据进行配对学生t检验)。虽然GHRP - 2测试的生长激素AUC与联合给予GHRH1 - 29NH2和GHRP - 2测试的生长激素AUC有显著差异(P = 0.016,t检验),但后者与各受试者单独测试后的生长激素AUC之和无显著差异。
虽然GHRP - 2的生长激素释放效力显著超过GHRH1 - 29NH2,但我们未能证明这两种物质之间存在协同作用。有可能我们研究中给予的GHRP - 2的摩尔量高于GHRH1 - 29NH2,从而掩盖了后者的作用。