Arvat E, Gianotti L, Grottoli S, Imbimbo B P, Lenaerts V, Deghenghi R, Camanni F, Ghigo E
Department of Clinical Pathophysiology, University of Turin, Italy.
J Clin Endocrinol Metab. 1994 Nov;79(5):1440-3. doi: 10.1210/jcem.79.5.7962341.
Although both spontaneous and stimulated GH secretion undergo an age-related decline, the secretory capacity of somatotrope cells is preserved in human aging. In the present study we compared the GH responses to hexarelin, GHRH, and the combined administration of hexarelin and GHRH or arginine in young and elderly subjects. Thirteen young (24- to 30-yr-old) and 16 elderly (65- to 84-yr-old) normal males were divided into 2 groups. The first group (7 young and 8 elderly subjects) received the following as single iv injections during 3 different treatment sessions: hexarelin (2 micrograms/kg), GHRH (2 micrograms/kg), or hexarelin (2 micrograms/kg) plus GHRH (2 micrograms/kg). The second group (6 young and 8 elderly subjects) was administered single iv injections of hexarelin (2 micrograms/kg) or hexarelin (2 micrograms/kg) plus arginine (0.5 g/kg) during 2 different treatment sessions. In both groups basal IGF-I levels in the elderly were lower than those in young subjects (114.5 +/- 18.7 vs. 211.5 +/- 19.1 micrograms/L; P < 0.001). In the first group the GH response to hexarelin was greater in young compared to elderly subjects (area under the curve from 0-120 = 4849 +/- 601 vs. 2112 +/- 683 micrograms.min/L; P < 0.001). GHRH elicited a lower GH response than that induced by hexarelin in both young (1455 +/- 102 micrograms/h.L; P < 0.02) and elderly subjects (563 +/- 87 micrograms/min.L; P < 0.02). GHRH potentiated the somatotrope response to hexarelin in both young (7725 +/- 503 micrograms/min.L; P < 0.02) and elderly subjects (3895 +/- 612 micrograms/min.L; P < 0.02), but to a lesser extent in the latter (P < 0.001). In the second group, the GH response induced by hexarelin was also higher in young subjects than in elderly subjects (4819 +/- 668 vs. 1649 +/- 459 micrograms/min.L; P < 0.001). The GH response to hexarelin was potentiated by arginine in elderly (4139 +/- 1057 micrograms/min. L; P < 0.001), but not in young subjects (4743 +/- 774 micrograms/min.L). This study shows that the maximal effective dose of hexarelin releases more GH than the maximal effective dose of GHRH in both normal young and elderly subjects. The effect of hexarelin on GH secretion is age dependent, and the GH response to the combined administration of hexarelin and GHRH was significantly higher in young subjects compared to elderly subjects. Arginine does not potentiate the GH response to hexarelin in young subjects, whereas it significantly enhances it in elderly subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
尽管自发性和刺激性生长激素（GH）分泌均随年龄增长而下降，但生长激素细胞的分泌能力在人类衰老过程中得以保留。在本研究中，我们比较了年轻和老年受试者对六肽生长激素释放肽（hexarelin）、生长激素释放激素（GHRH）以及六肽生长激素释放肽与生长激素释放激素联合给药或精氨酸的GH反应。13名年轻（24至30岁）和16名老年（65至84岁）正常男性被分为2组。第一组（7名年轻和8名老年受试者）在3个不同的治疗时段接受以下单次静脉注射：六肽生长激素释放肽（2微克/千克）、生长激素释放激素（2微克/千克）或六肽生长激素释放肽（2微克/千克）加生长激素释放激素（2微克/千克）。第二组（6名年轻和8名老年受试者）在2个不同的治疗时段接受单次静脉注射六肽生长激素释放肽（2微克/千克）或六肽生长激素释放肽（2微克/千克）加精氨酸（0.5克/千克）。两组中老年受试者的基础胰岛素样生长因子-I（IGF-I）水平均低于年轻受试者（114.5±18.7 vs. 211.5±19.1微克/升；P<0.001）。在第一组中，年轻受试者对六肽生长激素释放肽的GH反应大于老年受试者（0至120分钟曲线下面积=4849±601 vs. 2112±683微克·分钟/升；P<0.001）。生长激素释放激素在年轻（1455±102微克/小时·升；P<0.02）和老年受试者（563±87微克/分钟·升；P<0.02）中引发的GH反应均低于六肽生长激素释放肽。生长激素释放激素增强了年轻（7725±503微克/分钟·升；P<0.02）和老年受试者（3895±612微克/分钟·升；P<0.02）对六肽生长激素释放肽的生长激素细胞反应，但在老年受试者中程度较小（P<0.001）。在第二组中，年轻受试者中六肽生长激素释放肽诱导的GH反应也高于老年受试者（4819±668 vs. 1649±459微克/分钟·升；P<0.001）。精氨酸增强了老年受试者对六肽生长激素释放肽的GH反应（4139±1057微克/分钟·升；P<0.001），但在年轻受试者中未增强（4743±774微克/分钟·升）。本研究表明，在正常年轻和老年受试者中，六肽生长激素释放肽的最大有效剂量比生长激素释放激素的最大有效剂量释放更多的GH。六肽生长激素释放肽对GH分泌的影响具有年龄依赖性，与老年受试者相比，年轻受试者中六肽生长激素释放肽与生长激素释放激素联合给药的GH反应显著更高。精氨酸在年轻受试者中不增强对六肽生长激素释放肽的GH反应，而在老年受试者中显著增强。（摘要截断于400字）
