We have examined the contribution of transcriptional mechanisms to the pleiotropic effects of glucocorticoids on basal and vitamin D stimulated expression of the developmentally regulated bone-specific osteocalcin (OC) gene. OC expression was systematically investigated at the level of protein, mRNA
Regulation of human Gc (vitamin D — binding) protein levels: Hormonal and cytokine control of gene expression in vitro
✍ Scribed by Chandan Guha; Motoki Osawa; Phillip A. Werner; Robert M. Galbraith; Gary V. Paddock
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 982 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Studies were performed in Hep3B hepatocytes to better elucidate the mechanisms regulating circulating levels of human groupspecific component (Gc). We measured changes in Gc messenger RNA (mRNA) synthesis and levels of secreted protein resulting from treatment of hepatocytes with cytokines and hormones known to influence synthesis of other proteins of hepatic origin. We particularly focused on compounds known to be prototypic stimulants during the acute phase response. Interleukin-6 (IL-6) and dexamethasone were shown to increase Gc mRNA approximately twofold while transforming growth factor beta (TGFP) decreased Gc mRNA in a dose-dependent fashion by up to fivefold. The effects on secreted Gc protein levels were similar. These results indicate that Gc protein appears to be regulated differently than the other members of this gene family, albumin and alpha-fetoprotein (AFP), which are negative acute phase reactants. In addition, these contrasting effects on Gc synthesis of IL-6 and dexamethasone and of TGFP suggest that high basal levels of Gc synthesis may be maintained during the acute phase response. PA-
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