CHARACTERIZATION OF SOMATOTROPIN--RECEPTOR INTERACTIONS

促生长素（生长激素，GH），催乳素（PRL）和胎盘激素 催乳素（PL）形成一个结构和功能相关家族， 对年生长和新陈代谢重要的蛋白质。 的同源性 这些蛋白质也在与蛋白质相互作用的水平上表达。 细胞表面受体，但存在不同的特异性。 人GH（hGH） 有自己的特定灵长类动物体细胞受体， 动物的促体细胞激素和催乳激素受体。 很少有人了解 关于hGH与 受体或其作用机制，由于一些复杂的 因素（例如，生物活性污染物、难以进行的生物测定、多种形式 激素，受体群体异质性）。 以往的研究 胰岛素已经表明蛋白质碘化可以改变其活性 和/或对受体的亲和力。 由于大量的工作调查生长激素的行动 使用hGH的125 I-制剂，建议系统分离， 鉴别和表征标准品生成的hGH的125 I-碘代异构体 碘化程序。 凝胶过滤和高通量等技术 高效液相色谱法（HPLC），聚丙烯酰胺凝胶 电泳、等电聚焦和纸层析， 电泳和胰蛋白酶肽图谱将被用来 表征起始hGH和后续碘代异构体。 纯化的 示踪剂将进一步表征为与人淋巴细胞的结合， 兔乳腺膜和兔肝膜体细胞发生和 催乳素受体以及放射免疫测定和体外 使用制备的127 I-碘异构体进行催乳和促体生物测定。 HGH 在非灵长类动物中有活性，但非灵长类动物的GH在人类中没有活性，因此 用于临床治疗的hGH一直短缺 生长激素依赖性生长障碍 然而，现在，生物合成的甲硫氨酰-hGH （mhGH）在E.利用重组DNA技术， 正在进行测试以允许其临床使用。 mhGH的研究将是 与高纯度hGH平行进行，结果 对我们理解生长激素有很大的帮助 受体的相互作用，以及加速评估的关键 需要mGH。

The somatotropins (growth hormones, GH), prolactins (PRL) and placental lactogens (PL) form a family of structurally and functionally related proteins important for annual growth ad metabolism. Homologies between these proteins are also expressed at the level of interaction with cell-surface receptors, but distinct specificities exist. Human GH (hGH) has its own specific primate somatogenic receptor and will bind to both somatogenic and lactogenic receptors of animals. Little is well understood concerning the structure-function relationships of hGH interaction with receptor or its mechanism of action, due to a number of complicating factors (e.g. bioactive contaminants, difficult bioassays, multiple forms of the hormone, receptor population heterogeneity). Previous studies of insulin have indicated that iodination of a protein can alter its activity and/or affinity for receptor. Since much work investigating hGH action uses 125I-preparations of hGH, it is proposed to systematically isolate, identify and characterize the 125I-iodoisomers of hGH generated by standard iodination procedures. Techniques such as gel filtration and high performance liquid chromatography (HPLC), polyacrylamide gel electrophoresis, isoelectric focusing, and paper chromatography and electrophoresis, and tryptic peptide mapping will be employed to characterize the starting hGH and subsequent iodoisomers. The purified tracers will be further characterized for binding to human lymphocytes, rabbit mammary gland membrane and rabbit liver membrane somatogenic and lactogenic receptors as well as in radoimmunoassays, and in vitro lactogenic and somatogenic bioassays using prepared 127I-iodoisomers. HGH is active in nonprimates, but nonprimate GH is not active in man, thus there has been a shortage of hGH available for the clinical treatment of GH-dependent growth disorders. Now, however, biosynthetic methionyl-hGH (mhGH) synthesized in E. coli using recombinant DNA technology is undergoing testing to allow its use clinically. Studies of mhGH will be conducted in parallel with those of highly purified hGH and the results should contribute significantly to our understanding of somatotropin: receptor interactions, as well as hasten the evaluation of the critically needed mhGH.