PMID: 11916628Mar 28, 2002Paper

Effect of different growth hormone (GH) mutants on the regulation of GH-receptor gene transcription in a human hepatoma cell line

European Journal of Endocrinology
Johnny DeladoëyPrimus E Mullis

Abstract

G to A transition at position 6664 of the growth hormone (GH-1) gene results in the substitution of Arg183 by His (R183H) in the GH protein and causes a new form of autosomal dominant isolated GH deficiency (IGHD type II). The aim of this study was to assess the bioactivity of this R183H mutant GH in comparison with both other GH variants and the 22-kDa GH in terms of GH-receptor gene regulation. The regulation of the GH-receptor gene (GH-receptor/GH binding protein, GHR/GHBP) transcription following the addition of variable concentrations (0, 12.5, 25, 50 and 500 ng/ml) of R183H mutant GH was studied in a human hepatoma cell line (HuH7) cultured in a serum-free hormonally defined medium. In addition, identical experiments were performed using either recombinant human GH (22-kDa GH) as a positive control or two GH-receptor antagonists (R77C mutant GH and pegvisomant (B-2036-PEG)) as negative controls. GHR/GHBP mRNA expression was quantitatively assessed by RT-PCR amplification after 0, 1, 3 and 6 h incubation. Following the addition of R183H mutant GH, GHR/GHBP mRNA changed at a similar rate to that seen in experiments where 22-kDa GH was added, indicating equal bioactivity. At all times and concentrations studied, the addition...Continue Reading

Citations

Dec 20, 2005·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Sanne Fisker
Aug 6, 2003·The Journal of School Health·Susan C Hill, Gordon B Lindsay
Dec 7, 2005·Oncogene·R MuromotoT Matsuda
May 24, 2007·The Journal of Clinical Endocrinology and Metabolism·Vibor PetkovicPrimus E Mullis

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