Martínez-Coria Hilda, López-Rosales L Javier, Carranza Martha, Berumen Laura, Luna Maricela, Arámburo Carlos
Department of Neuroendocrinology, Centro de Neurobiología, Universidad Nacional Autónoma de Mexico, Querétaro.
Endocrine. 2002 Mar;17(2):91-102. doi: 10.1385/ENDO:17:2:91.
Variants of growth hormone (GH) are present in most vertebrates. Chicken GH (cGH) undergoes posttranslational modifications that contribute to its structural diversity. Although the 22-kDa form of GH is the most abundant, some other variants have discrete bioactivities that may not be shared by others. The proportion of cGH variants changes during ontogeny, suggesting that they are regulated differentially. The effect of growth hormone-releasing hormone (GHRH) on the release of cGH variants was studied in both pituitary gland and primary cell cultures, employing sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, and densitometry. GHRH (2 nM, 2 h) stimulated the secretion of most of the size variants of cGH although the amplitude of increase was not equal for each one. A differential effect on the secretion of GH size variants, particularly on the 22- (monomer) and 26-kDa (putatively glycosylated) cGH isoforms was found in both systems. In the whole pituitary culture, the proportion of the 26-kDa immunoreactive cGH increased 35% while the 22 kDa decreased 31% after GHRH treatment in comparison with the controls. In the primary cell culture system, the proportion of the glycosylated variant increased 43% whereas the monomer and the dimer decreased 22.26 and 29%, respectively, after GHRH stimulation. Activators of intracellular signals such as 1 mM 8-bromo-cAMP and 1 microM phorbol myristate acetate had a similar effect to that obtained with GHRH. The data support the hypothesis that GH variants may be under differential control and that GHRH promotes the release of a glycosylated cGH variant that has an extended half-life in circulation.
大多数脊椎动物体内都存在生长激素（GH）变体。鸡生长激素（cGH）会经历翻译后修饰，这促成了其结构多样性。尽管22 kDa形式的GH最为丰富，但其他一些变体具有独特的生物活性，可能不为其他变体所共有。cGH变体的比例在个体发育过程中会发生变化，这表明它们受到不同的调控。我们采用十二烷基硫酸钠聚丙烯酰胺凝胶电泳、蛋白质免疫印迹法和光密度测定法，在垂体和原代细胞培养物中研究了生长激素释放激素（GHRH）对cGH变体释放的影响。GHRH（2 nM，2小时）刺激了大多数cGH大小变体的分泌，尽管每个变体的增加幅度并不相同。在这两种系统中均发现，GHRH对GH大小变体的分泌有差异效应，特别是对22 kDa（单体）和26 kDa（可能糖基化）的cGH同工型。在整个垂体培养物中，与对照组相比，GHRH处理后26 kDa免疫反应性cGH的比例增加了35%，而22 kDa的比例下降了31%。在原代细胞培养系统中，GHRH刺激后，糖基化变体的比例增加了43%，而单体和二聚体分别下降了22.26%和29%。细胞内信号激活剂，如1 mM 8-溴-cAMP和1 microM佛波醇肉豆蔻酸酯乙酸盐，具有与GHRH类似的作用。这些数据支持以下假设：GH变体可能受到不同的控制，并且GHRH促进了一种糖基化cGH变体的释放，该变体在循环中的半衰期延长。
