Endocrine Abstracts

Obesity is associated with hypothalamic-pituitary-adrenal (HPA) axis activation. In obese humans and leptin-resistant obese Zucker rats, we have reported increased excretion of A-ring reduced glucocorticoid metabolites. We have now investigated regulation of hepatic A-ring reductases in the obese Zucker rat.Lean and obese Zucker rats (9wks) were studied either: 3-weeks after adrenalectomy (ADX) or sham surgery; or after 3-weeks treatment with metformin ...

Metabolism of glucocorticoids to dihydro and tetrahydro derivatives via hepatic 5alpha- and 5beta-reductases has been assumed to be a pathway of irreversible inactivation of glucocorticoids. However, 5alpha-reduced metabolites of other steroids (testosterone, aldosterone) have significant affinity for the parent hormone receptor. We have investigated whether 5alpha-reduced metabolites of corticosterone (B) are GR agonists.In hepatocytes from male lean Zucker rats (n=6) com...