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 alpha-helix in bovine GH (bGH) was investigated. A GH analog (bGH-M8), in which three amino acids were substituted to form an idealized amphiphilic alpha-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 alpha-helix of bGH, which is independent of amino acids important in the initial interaction of GH with its receptor.
authors.affiliation: Department of Zoological and Biomedical Sciences, Ohio University, Athens 45701.
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: W Y
authors.initials: WY
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Wiehl
authors.forename: B
authors.initials: B
authors.lastname: Kelder
authors.forename: H M
authors.initials: HM
authors.lastname: Goodman
authors.forename: S
authors.initials: S
authors.lastname: Guller
authors.forename: M
authors.initials: M
authors.lastname: Sonenberg
authors.forename: J J
authors.initials: JJ
authors.lastname: Kopchick
mesh_terms: D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D013006:Growth Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors*; D007328:Insulin / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D051381:Rats
chemical_list: D007328:Insulin; D013006:Growth Hormone