Endocrine Abstracts

Introduction: In humans, Cushing’s syndrome (CS) is associated with an increased incidence of the metabolic syndrome, increased cardiovascular morbidity and mortality, even after long-term correction of glucocorticoid (GC) excess.

Aim: To evaluate the effects of transient overexposure to GC on the metabolic changes in the long-term in mice.

Methods: Single housed male C57Bl/6J mice were given corticosterone (CORT; 50 μg/ml) or vehicle in the drinking water for 4 weeks, followed by a washout period for 4 or 8 weeks thereafter. Plasma circadian corticosterone levels were assessed at baseline, and at weeks 4, 8, and 12 after the start of exposure. Lipids, insulin, and glucose levels were measured after an overnight fast. Insulin sensitivity was assessed by hyperinsulenemic-euglycemic clamp at week 8 and 12, lean and body- and fat mass by DEXA analysis.

Results: CORT-treatment transiently increased plasma corticosterone by 37-, 13-, 3- and 13-fold at 0700, 1200, 1800 and 2200 h respectively. At week 8, evening peak CORT levels (1800 h) were suppressed, which returned to baseline levels at week 12. CORT-treatment increased food intake and plasma levels of insulin, trigycerides, free fatty acids and cholesterol. Abrogation of CORT normalized food intake, whereas body weight remained unchanged. At week 12, insulin was still significantly higher in CORT treated mice. There were no differences in the lean body or fat mass at week 8 and 12 weeks. Hyperinsulinemic–euglycemic clamp indicated no changes in CORT-treated mice at week 8 or 12.

Conclusion: In mice, transient glucocorticoid excess does not cause persisting metabolic changes. Recovery of these metabolic changes coincides with recovery of the HPA-axis.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.