Metabolic effects of 5α-reductase 1 disruption
Isoforms of 5α-reductase regulate the production of steroid hormones and metabolites. In male mice, global deletion of 5α-reductase type 1 resulted in obesity and insulin resistance, with increased susceptibility to liver steatosis, fibrosis and hepatocellular carcinoma, but questions remained as to the relative contribution of androgens or glucocorticoid signalling in phenotype development.
Livingstone et al. therefore examined the role of 5α-reductase type 1 deficiency in females on metabolic parameters, using a transgenic knockout approach. Altered stress responses were observed in females with 5α-reductase type 1 deficiency, with decreased corticosterone production in response to restraint, and decreased corticotrophin-releasing hormone (CRH) and arginine vasopressin transcript expression in hypothalamic nuclei, as well as reduced CRH receptor expression in the pituitary. Metabolic profiling showed increased body weight and adiposity in 5α-reductase knockout females, with changes in hepatic weight and lipid profile with ageing.
Read the full article in Journal of Endocrinology 232 29–36