Micić D, Kendereski A, Popović V, Sumarac M, Zorić S, Macut D, Dieguez C, Casanueva F
Institute of Endocrinology, Diabetes and Diseases of Metabolism, Beograd, Yugoslavia.
Clin Endocrinol (Oxf). 1996 Oct;45(4):385-90. doi: 10.1046/j.1365-2265.1996.8380848.x.
Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. A defect in the regulation of GH secretion has been suggested in PCOS but the available data are limited and the underlying mechanisms remain unknown. In recent years considerable attention has been devoted to non-classic GH secretagogues and, in particular, to the series of hexapeptides of which GH-releasing peptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, known as GHRP-6) is the most representative. GHRP-6 seems to be a promising tool for exploring GH secretory mechanisms and it has been reported that GHRH + GHRP-6 is a powerful stimulus to GH secretion. Our aim was to investigate the GH responses to GHRH, GHRP-6 and the administration of GHRP + GHRP-6 in two groups of patients (normal weight and obese) with PCOS in comparison with matched control groups.
All subjects were studied three times on different days with GHRH (100 micrograms i.v.), GHRP-6 (90 micrograms i.v.) and GHRH + GHRP-6 (100 micrograms + 90 micrograms).
Sixteen women with PCOS and 22 healthy controls were studied. They were divided into four groups according to BMI: Group A (non-obese PCOS, n = 6, age 21.8 +/- 1.7 years, BMI 22.1 +/- 0.8 kg/m2); Group B: (obese PCOS, n = 10, age 21.7 +/- 1.3 years, BMI 32.9 +/- 2.1 kg/m2); Group C (non-obese healthy women, n = 13, age 26.8 +/- 1.5 years, BMI 21.8 +/- 0.6 kg/m2) and Group D (obese healthy women, n = 9, age 29.4 +/- 4.2 years, BMI 35.7 +/- 1.3 kg/m2).
Serum GH was measured using a time-resolved fluoroimmunoassay (Delphia, Pharmacia).
After GHRH administration significant differences were found between GH peaks in Groups A and B (82.4 +/- 16.4 vs 20 +/- 4.9 mU/l, P < 0.05) and in AUC for GH between Groups A and B (4667 +/- 1061 vs 947 +/- 236, P < 0.05) while there were no differences between the same groups in GH peak or AUC after GHRP-6 administration. There were no significant differences in peaks or AUC for GH after GHRH between Groups A and C, nor between Groups B and D. There were significant differences in GH peaks after combined administration of GHRH + GHRP-6 between Groups A and B (211 +/- 26.4 vs 108 +/- 17.6, P < 0.05) as well as between GH AUC in Groups A and B (12068 +/- 2323 vs 5997 +/- 1342, P < 0.05). There were no differences in GH peaks or AUC for GH after GHRH + GHRP-6 administration between Groups A and C or Groups B and D.
The impaired GH response to GHRH found in obese PCOS patients is a consequence of obesity and could be a functional defect, since it can be overridden with GHRP-6 administration.
尽管诊断设备有所改进且体外研究取得进展，但多囊卵巢综合征（PCOS）的主要病因仍未明确。有研究提示PCOS患者存在生长激素（GH）分泌调节缺陷，但现有数据有限，其潜在机制仍不清楚。近年来，非经典GH促分泌素受到了广泛关注，尤其是一系列六肽，其中生长激素释放肽（His-D-Trp-Ala-Trp-D-Phe-Lys-NH2，即GHRP-6）最具代表性。GHRP-6似乎是探索GH分泌机制的一个有前景的工具，据报道，生长激素释放激素（GHRH）+GHRP-6是GH分泌的有力刺激因素。我们的目的是研究两组PCOS患者（正常体重和肥胖）与匹配对照组对GHRH、GHRP-6以及GHRH+GHRP-6联合给药的GH反应。
所有受试者在不同日期接受三次研究，分别给予GHRH（静脉注射100微克）、GHRP-6（静脉注射90微克）和GHRH+GHRP-6（100微克+90微克）。
研究了16例PCOS女性和22例健康对照者。根据体重指数（BMI）将他们分为四组：A组（非肥胖PCOS，n = 6，年龄21.8±1.7岁，BMI 22.1±0.8 kg/m²）；B组（肥胖PCOS，n = 10，年龄21.7±1.3岁，BMI 32.9±2.1 kg/m²）；C组（非肥胖健康女性，n = 13，年龄26.8±1.5岁，BMI 21.8±0.6 kg/m²）和D组（肥胖健康女性，n = 9，年龄29.4±4.2岁，BMI 35.7±1.3 kg/m²）。
采用时间分辨荧光免疫分析法（Pharmacia公司的Delphia）测定血清GH。
给予GHRH后，A组和B组的GH峰值存在显著差异（82.4±16.4对20±4.9 mU/l，P<0.05），A组和B组的GH曲线下面积（AUC）也存在显著差异（4667±1061对947±236，P<0.05），而给予GHRP-6后，相同两组的GH峰值或AUC无差异。A组和C组、B组和D组在给予GHRH后的GH峰值或AUC无显著差异。A组和B组在联合给予GHRH+GHRP-6后的GH峰值存在显著差异（211±26.4对108±17.6，P<0.05），A组和B组的GH AUC也存在显著差异（1206±2323对5997±1342，P<0.05）。A组和C组、B组和D组在给予GHRH+GHRP-6后的GH峰值或AUC无差异。
肥胖的PCOS患者对GHRH的GH反应受损是肥胖的结果，可能是一种功能缺陷，因为给予GHRP-6可克服这一缺陷。
