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通过定点诱变对人生长激素进行选择性修饰:对生物活性多样性的影响。

Selective modification of human growth hormone by site-directed mutagenesis: implications for the diversity of biological actions.

作者信息

Tchelet A, Gertler A, Sakal E, Djiane J, Vogel T

机构信息

Department of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, Hebrew University of Jerusalem, Rehovot, Israel.

出版信息

Horm Res. 1994;41 Suppl 2:103-12. doi: 10.1159/000183969.

DOI:10.1159/000183969
PMID:8088697
Abstract

Human growth hormone (GH) is an anabolic hormone required for normal growth. In addition, human GH affects the metabolism of proteins, carbohydrates and fats and possesses lactogenic effects. Although the GH receptor has recently been cloned, it is not clear whether the diverse biological activities of human GH are transduced through a single or through several types of related receptors. To address this question, 15 recombinant analogues of human GH were prepared and tested in bioassays in vitro and in vivo, in which the hormone action is mediated through lactogen or somatogen receptors. The results clearly suggest that recombinant analogues of human GH that recognize either somatogen or lactogen receptors, or both, but have selectively modified post-receptor effects, are helpful in elucidating the diverse biological activities of GH. These differences are most probably due to minor structural variability in GH and lactogen receptors in different organs and/or species. Genetic engineering of human GH may lead to production of modified analogues with changed and narrower specificities. One of the possible applications would be for a human GH analogue devoid of diabetogenic activity.

摘要

人生长激素(GH)是正常生长所需的一种合成代谢激素。此外,人生长激素还影响蛋白质、碳水化合物和脂肪的代谢,并具有催乳作用。尽管最近已克隆出GH受体,但尚不清楚人生长激素的多种生物学活性是通过单一类型还是几种相关受体转导的。为了解决这个问题,制备了15种人生长激素重组类似物,并在体外和体内生物测定中进行了测试,其中激素作用是通过催乳素或生长激素受体介导的。结果清楚地表明,能识别生长激素或催乳素受体或两者,但具有选择性修饰的受体后效应的人生长激素重组类似物,有助于阐明生长激素的多种生物学活性。这些差异很可能是由于不同器官和/或物种中生长激素和催乳素受体的微小结构变异性所致。人生长激素的基因工程可能会导致产生具有改变和更窄特异性的修饰类似物。一种可能的应用是用于一种无致糖尿病活性的人生长激素类似物。

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Horm Res. 1994;41 Suppl 2:103-12. doi: 10.1159/000183969.
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Differential effects of maternal ovine placental lactogen and growth hormone (GH) administration on GH receptor, insulin-like growth factor (IGF)-1 and IGF binding protein-3 gene expression in the pregnant and fetal sheep.母体给予绵羊胎盘催乳素和生长激素(GH)对妊娠和胎儿绵羊生长激素受体、胰岛素样生长因子(IGF)-1及IGF结合蛋白-3基因表达的差异影响。
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Growth Factors. 2005 Mar;23(1):55-66. doi: 10.1080/08977190500055851.

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