5α-Reduced Glucocorticoids: A Story of Natural Selection

The document from 2011 reviews the potential of 5α-reduced glucocorticoids (GCs) as anti-inflammatory steroids with fewer metabolic side effects compared to current synthetic GCs. It discusses the cloning and characterization of 5α-reductase isozymes, SRD5A1 and SRD5A2, and their role in steroid metabolism, male reproductive system development, and their association with diseases like prostate cancer and PCOS. The metabolism of GCs by these isozymes is explored, noting that human isozymes poorly metabolize GCs but produce metabolites with distinct anti-inflammatory properties. The document also highlights the importance of the balance between parent GCs and their metabolites, especially in the liver, and suggests that 5α-reduced GCs could be prototypes for drug design. However, it raises concerns about the effects of 5α-reductase inhibitors on this balance and potential adverse metabolic and inflammatory effects. The work acknowledges various grants and assistance with chemical figures.