5α-Reductase Type 2 Regulates Glucocorticoid Action and Metabolic Phenotype in Human Hepatocytes

The study investigated the role of 5α-reductase type 2 (SRD5A2) in regulating glucocorticoid and androgen action on lipid metabolism in human hepatocytes, involving primary cells from 8 donors. It found that SRD5A2 influenced glucocorticoid metabolism, affecting liver cell metabolic phenotype. Androgens increased lipogenesis, with testosterone enhancing it in females but not males, while dihydrotestosterone decreased it in females. Glucocorticoids decreased lipogenesis dose-dependently but increased insulin-stimulated lipogenesis. Overexpression of SRD5A2 reduced cortisol's suppression of lipogenesis, an effect reversed by finasteride and dutasteride. The study suggested SRD5A2 as a potential target for metabolic disorder therapies and raised concerns about 5α-reductase inhibitors' impact on liver metabolism.