Tsushima T, Katoh Y, Miyachi Y, Chihara K, Teramoto A, Irie M, Hashimoto Y
Department of Medicine 2, Tokyo Women's Medical University, Japan.
J Clin Endocrinol Metab. 1999 Jan;84(1):317-22. doi: 10.1210/jcem.84.1.5395.
Several GH isoforms have been identified in pituitary and serum, the most abundant of which is the 22K human GH (hGH) isoform. The 20K hGH isoform is produced by alternative splicing of GH messenger ribonucleic acid and comprises approximately 10% of all GH in the pituitary. The physiological role of 20K hGH remains to be determined, partly because of the lack of a simple and specific assay. We have established sensitive enzyme-linked immunosorbent assays (ELISAs) specific to 20K and 22K hGH. To determine whether regulation of 20K hGH secretion is the same as that for 22K hGH, we measured serum concentrations of both species of hGH in normal subjects and patients with a variety of endocrine disorders. The serum levels of 20K hGH after overnight fasting was 118 +/- 178 pg/mL (n = 282) in normal women, significantly higher than that in normal men (64 +/- 170 pg/mL; n = 226). However, there was no difference in the proportion of 20K hGH to 20K plus 22K hGH between men (6.3 +/- 2.6%, mean +/- SD; n = 176) and women (6.3 +/- 2.1%; n = 263). No correlation was detected between the ratio of 20K hGH and age, body height, body weight, or body fat mass in normal subjects. The proportion of 20K hGH was significantly (P < 0.001) higher in patients with active acromegaly (9.2 +/- 2.2%; n = 33) and patients with anorexia nervosa (9.0 +/- 1.9; n = 8), both of which are characterized by chronic elevation of circulating GH levels. The proportion of 20K hGH in successfully treated acromegalic patients did not differ from that in normal subjects, suggesting that GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or that a chronic excess of 22K hGH alters the MCR of 20K hGH. The values in patients with adult GH deficiency, hyperthyroidism, primary hypothyroidism, or GH-independent short stature did not differ from those in normal subjects. The 20K ratio did not change after acute GH provocative tests, such as the insulin tolerance test and the GHRH test. These results suggest that secretion of 20K hGH from the pituitary is under the same control as that of 22K hGH. This new assay may provide a tool for understanding the physiological or pathophysiological role of the 20K hGH isoform.
在垂体和血清中已鉴定出几种生长激素(GH)同工型,其中含量最丰富的是22K人类生长激素(hGH)同工型。20K hGH同工型是由GH信使核糖核酸的可变剪接产生的,约占垂体中所有GH的10%。20K hGH的生理作用尚待确定,部分原因是缺乏简单而特异的检测方法。我们已经建立了针对20K和22K hGH的灵敏酶联免疫吸附测定法(ELISA)。为了确定20K hGH分泌的调节是否与22K hGH相同,我们测量了正常受试者和患有各种内分泌疾病患者血清中这两种hGH的浓度。正常女性过夜禁食后20K hGH的血清水平为118±178 pg/mL(n = 282),显著高于正常男性(64±170 pg/mL;n = 226)。然而,男性(6.3±2.6%,平均值±标准差;n = 176)和女性(6.3±2.1%;n = 263)中20K hGH占20K加22K hGH的比例没有差异。在正常受试者中,未检测到20K hGH与年龄、身高、体重或体脂量之间的相关性。在活动性肢端肥大症患者(9.2±2.2%;n = 33)和神经性厌食症患者(9.0±1.9;n = 8)中,20K hGH的比例显著更高(P < 0.001),这两种疾病的特征都是循环GH水平长期升高。成功治疗的肢端肥大症患者中20K hGH的比例与正常受试者没有差异,这表明产生GH的垂体肿瘤分泌的20K hGH比例更高,或者慢性过量的22K hGH改变了20K hGH的代谢清除率(MCR)。成年生长激素缺乏症、甲状腺功能亢进症、原发性甲状腺功能减退症或非生长激素依赖性身材矮小患者的值与正常受试者没有差异。在急性生长激素激发试验,如胰岛素耐量试验和生长激素释放激素(GHRH)试验后,20K比例没有变化。这些结果表明,垂体中20K hGH的分泌与22K hGH受相同的控制。这种新的检测方法可能为理解20K hGH同工型的生理或病理生理作用提供一种工具。