Regulation of the Metabolic Phenotype of Human Hepatocytes by Glucocorticoids and Androgens

The study investigated the role of glucocorticoids and androgens, and their metabolism by the enzyme 5αR2 (SRD5A2), on lipid homeostasis in human hepatocytes. It was found that glucocorticoids decreased de novo lipogenesis in a dose-dependent manner, while androgens increased lipogenesis in female hepatocytes but had no effect in male hepatocytes. Overexpression of SRD5A2 reduced the suppressive effects of cortisol on lipogenesis, an effect that was negated by an inactive mutant construct. Inhibition of 5αR2 with finasteride and dutasteride enhanced cortisol's action. The findings suggested that manipulating 5αR2 activity could regulate lipogenesis, with potential clinical implications for patients using 5αR inhibitors, particularly in enhancing glucocorticoid effects on hepatic lipid metabolism.