A growth hormone (GH) analog can antagonize the ability of native GH to promote differentiation of 3T3-F442A preadipocytes and stimulate insulin-like and lipolytic activities in primary rat adipocytes Journal Article
| Authors: | Okada, S.; Chen, W. Y.; Wiehl, P.; Kelder, B.; Goodman, H. M.; Guller, S.; Sonenberg, M.; Kopchick, J. J. |
| Article Title: | A growth hormone (GH) analog can antagonize the ability of native GH to promote differentiation of 3T3-F442A preadipocytes and stimulate insulin-like and lipolytic activities in primary rat adipocytes |
| Abstract: | The effect of amino acid substitutions introduced to the third α-helix in bovine GH (bGH) was investigated. A GH analog (bGH-M8), in which three amino acids were substituted to form an idealized amphiphilic α-helix, possessed the same specific binding affinity as wild-type bGH to cell membranes prepared from 3T3-F442A cells or rat adipocytes. However, bGH-M8 failed to stimulate preadipocyte differentiation, as measured by the level of glycerol-3-phosphate dehydrogenase activity. An equimolar concentration of bGH-M8 was inhibitory for this adipogenic effect caused by bGH at a concentration of 30 pM. bGH-M8 also failed to induce an insulin-like response and reduced lipolytic potency in rat primary adipocytes. A 10-fold excess of bGH-M8 abolished the effect of wild-type bGH in the insulin-like and lipolytic assays. Thus, bGH-M8 inhibited these actions of wild-type bGH and, therefore, appears to be a competitive antagonist. These results suggest that a major biologically active domain resides in the third α-helix of bGH, which is independent of amino acids important in the initial interaction of GH with its receptor. © 1992 by The Endocrine Society. |
| Keywords: | nonhuman; binding affinity; animal cell; animal; mice; cells, cultured; amino acid substitution; cell differentiation; growth hormone; rat; insulin; rats; cell strain 3t3; adipose tissue; 3t3 cells; carbon dioxide; adipocyte; hormone antagonist; proadipocyte; lipolysis; male; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; insulin like activity; glycerol 3 phosphate dehydrogenase; growth hormone derivative |
| Journal Title: | Endocrinology |
| Volume: | 130 |
| Issue: | 4 |
| ISSN: | 0013-7227 |
| Publisher: | Endocrine Society |
| Date Published: | 1992-04-01 |
| Start Page: | 2284 |
| End Page: | 2290 |
| Language: | English |
| DOI: | 10.1210/endo.130.4.1547740 |
| PUBMED: | 1547740 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 30 July 2019 -- Source: Scopus |
