生长激素增加而胰岛素样生长因子-I降低循环脂蛋白(a)。

Growth hormone increases and insulin-like growth factor-I decreases circulating lipoprotein(a).

作者信息

Laron Z, Wang X L, Klinger B, Silbergeld A, Wilcken D E

机构信息

Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center, Israel.

出版信息

Eur J Endocrinol. 1997 Apr;136(4):377-81. doi: 10.1530/eje.0.1360377.

DOI:10.1530/eje.0.1360377

PMID:9150696

Abstract

BACKGROUND

Elevated serum lipoprotein(a) (Lp(a)) is a strong risk factor for coronary artery disease (CAD). Genetic factors appear to account for the major variance in Lp(a) levels but the contribution hormones make in modulating Lp(a) levels is not yet clear. In the present investigation we determined the effects of human growth hormone (hGH) and insulin-like growth factor-I (IGF-I) on circulating Lp(a).

METHODS

Four groups of patients were studied. Group a: adults with GH deficiency (n = 7) treated with hGH (0.05 U/kg/day, s.c.); group b: girls with Turner syndrome (n = 7) treated with hGH (0.1 U/kg/day, s.c.); group c: prepubertal boys with idiopathic short stature (n = 6) treated with the GH secretagogue (GHRP) hexarelin (60 micrograms t.i.d. intranasally); group d: Laron syndrome patients (n = 10) treated with IGF-I (100-200 micrograms/kg/day, s.c.). Following overnight fasting, serum was sampled before the initiation of treatment and during 6-9 months treatment.

RESULTS

Serum IGF-I rose significantly in all the subjects in all four groups. In the first three groups in which IGF-I was elevated by exogenous or endogenous GH stimulation, serum Lp(a) increased significantly (119 +/- 35%, P < 0.01; 126 +/- 44%, P < 0.05; 102 +/- 29%, P < 0.01 for groups a, b, and c respectively). By contrast, serum Lp(a) levels decreased in group d to whom exogenous IGF-I was administered (-66 +/- 5%, P < 0.001). The differential effect of endogenous vs exogenous IGF-I on serum Lp(a) paralleled the behaviour of serum insulin. Insulin was significantly increased in all the subjects receiving hGH or GHRP (65.2 +/- 31%, P = 0.109; 93.7 +/- 53%, P = 0.062; 353.8 +/- 52.7%, P < 0.01 for groups a, b, and c respectively) whereas insulin levels were reduced following exogenous administration of IGF-I (-34.1 +/- 9.1%, P < 0.01).

CONCLUSIONS

We conclude that long-term GH treatment increases and IGF-I decreases circulating levels of Lp(a). These findings may have clinical relevance in view of the increasing use of hGH in children and adults and the role of Lp(a) as a CAD risk factor.

摘要

背景

血清脂蛋白(a)[Lp(a)]水平升高是冠状动脉疾病（CAD）的一个重要危险因素。遗传因素似乎是Lp(a)水平差异的主要原因，但激素在调节Lp(a)水平中的作用尚不清楚。在本研究中，我们测定了人生长激素（hGH）和胰岛素样生长因子-I（IGF-I）对循环Lp(a)的影响。

方法

对四组患者进行了研究。A组：生长激素缺乏的成年人（n = 7），接受hGH治疗（0.05 U/kg/天，皮下注射）；B组：特纳综合征女孩（n = 7），接受hGH治疗（0.1 U/kg/天，皮下注射）；C组：青春期前特发性身材矮小的男孩（n = 6），接受生长激素促分泌素（GHRP）六肽生长激素释放肽（60微克，每日三次，鼻内给药）治疗；D组：拉伦综合征患者（n = 10），接受IGF-I治疗（100 - 200微克/千克/天，皮下注射）。过夜禁食后，在治疗开始前及治疗6 - 9个月期间采集血清样本。

结果

所有四组患者的血清IGF-I均显著升高。在前三组中，IGF-I通过外源性或内源性生长激素刺激而升高，血清Lp(a)显著增加（A组、B组和C组分别为119±35%，P < 0.01；126±44%，P < 0.05；102±29%，P < 0.01）。相比之下，接受外源性IGF-I治疗的D组血清Lp(a)水平下降（-66±5%，P < 0.001）。内源性与外源性IGF-I对血清Lp(a)的不同影响与血清胰岛素的变化情况相似。接受hGH或GHRP治疗的所有患者胰岛素均显著升高（A组、B组和C组分别为65.2±31%，P = 0.109；93.7±53%，P = 0.062；353.8±52.7%，P < 0.01），而外源性给予IGF-I后胰岛素水平降低（-34.1±9.1%，P < 0.01）。