In vitro and in vivo studies of antagonistic effects of human growth hormone analogs
| Autor: | W Y, Chen, N Y, Chen, J, Yun, T E, Wagner, J J, Kopchick |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
Sequence Homology Amino Acid Body Weight Molecular Sequence Data Mice Inbred Strains Mice Transgenic Receptors Somatotropin Phosphoproteins Transfection Cell Line Mice Inbred C57BL Kinetics Mice Radioligand Assay L Cells Growth Hormone Multigene Family Mutagenesis Site-Directed Animals Humans Female Amino Acid Sequence Lymphocytes Insulin-Like Growth Factor I Phosphorylation |
| Zdroj: | The Journal of biological chemistry. 269(22) |
| ISSN: | 0021-9258 |
| Popis: | A bovine growth hormone (bGH) analog, bGH-G119R, has been shown to act as a functional antagonist of GH activity both in vitro and in vivo. In the present study, human (h) GH analogs with alterations in the third alpha-helix (G120A, G120R) and N terminus (I4A) were generated. These two regions have been reported to form binding site 2 in hGH, which is involved in in vitro dimerization of the GH receptor (GHR). The biological activities of these hGH analogs were tested in vitro by a radioreceptor assay and an assay to test the ability of the molecules to induce tyrosine phosphorylation of a 93-kDa protein in a human lymphocyte line, IM-9. The growth rate of transgenic mice that express different hGH analogs was used as an in vivo test of the activity of the molecules. The results demonstrated that G120R is a potent hGH antagonist both in vitro and in vivo. Transgenic mice expressing G120R demonstrated a growth-suppressed phenotype. However, I4A, which has been demonstrated to be a potent inhibitor of in vitro GHR dimerization, exhibited full growth promoting activity in transgenic mice. Thus, the ability of hGH analogs to induce GHR dimerization in vitro and the ability to promote growth in vivo are not directly correlated. |
| Databáze: | OpenAIRE |
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