Glucocorticoids are metabolised by 11-hydroxysteroid dehydrogenase 1 (11HSD1) and the A-ring reductases (5- and 5-reductases). Dysregulation of these enzymes has been reported in liver and adipose tissue in obese humans and animals, potentially leading to altered intracellular glucocorticoid concentrations and compensatory activation of the hypothalamic-pituitary-adrenal axis. This dysregulation of glucocorticoid metabolism in obesity is poorly understood. We hypothesised that changes in glucocorticoid metabolism in obesity are mediated by alterations in androgen action.

Steroid metabolism was studied in obese and lean male Zucker rats (age 10 weeks, n = 10/group) animals, 3 weeks after gonadectomy or sham surgery. Oral glucose tolerance tests were performed and activities and abundances of mRNAs for steroid metabolising enzymes were quantified in liver and adipose tissue.

Gonadectomy did not consistently alter weight gain, glucose intolerance or hyperinsulinemia in obese animals. Gonadectomy increased adrenal mass (P < 0.05), suppressed 11HSD1 activity and/or mRNA in liver and adipose, increased 5-reductase 1 mRNA in liver (P < 0.05), and increased 5-reductase activity only in obese animals (P < 0.05). Differences in hepatic 11HSD1 mRNA expression and adipose activity between lean and obese animals were normalised by gonadectomy, whereas obese gonadectomised animals maintained elevated liver 5-reductase and had an exaggerated elevation of 5-reductase activity.

We conclude that androgens tonically increase 11HSD1 in liver and adipose tissue in male rats, and contribute to the dysregulation of 11HSD1 in obesity. By contrast, androgens tonically suppress hepatic A-ring reductases in male rats, and do not contribute to dysregulation of these enzymes in obesity.