Growth Hormone Inhibits the 11β-Hydroxysteroid Dehydrogenase Type 1 Gene Promoter Activity via Insulin-like Growth Factor I in HepG2 Cells

Introduction

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), which is highly expressed in liver and adipose tissue, acts predominantly as an 11β-reductase in intact cells and in vivo, catalyzing the conversion of cortisone (E) to cortisol (F) [1].

11β-HSD1 enzyme has attracted great interest in recent years due to its potential importance in the development of metabolic syndrome. Transgenic mice overexpressing 11β-HSD1 in white adipose tissue develop central obesity, insulin resistance, and dyslipidemia [2]. In contrast, 11β-HSD1 knockout mice exhibit improved hepatic insulin sensitivity and lipid profiles [3]. 11β-HSD1 inhibition has exhibited favorable effects on the improvement of metabolic syndrome, which is thought to be a consequence of decreased intrahepatic glucocorticoids (GCs) regeneration by 11β-HSD1 oxoreductase [4].

Clinical studies have demonstrated that growth hormone (GH) inhibits 11β-HSD1 activity by measuring urine cortisol and cortisone metabolites [5]. However, there are few in vitro studies on the regulation of 11β-HSD1 gene expression by GH. In the present study, we used human hepatoma cell line HepG2 cells to investigate the effect of GH treatment on the transcriptional modulation of 11β-HSD1 by assaying gene promoter activity.

References

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