Dysregulation of vitamin D metabolism in the brain and myocardium of rats following prolonged exposure to dexamethasone

Abstract

Rationale: Chronic stress or hypercortisolism may increase the risks of depression, cardiac disorders, and osteoporosis, which are also associated with vitamin D (VD) deficiency. Both glucocorticoid receptor (GR) and vitamin D receptor (VDR) are widely distributed and affect many aspects of human physiology. The cross talk between the two steroids is pervasive, but the effect of glucocorticoids on circulating VD and local VD metabolism remains elusive.

Objectives: To fill this critical gap, we assessed the alterations of circulating VD and VD intracrine system in the brain and myocardium of rats treated with two different doses (0.2 and 2 mg/kg/day, respectively) of dexamethasone (Dex).

Results: Daily treatment with 2 mg/kg of Dex for 10 days induced the rats to a depressive-like state and decreased the expression of both VDR and the cytochromes P450 enzymes involved in VD activation (CYP27B1) and catabolism (CYP24A1) in the prefrontal cortex and hippocampus. Meanwhile, the dose of 0.2 mg/kg Dex increased the expression of VDR in the prefrontal cortex but inhibited CYP27B1/CYP24A1/VDR expression in the hippocampus. Similarly, in the myocardium, the rats treated with Dex showed significantly lower expression of CYP27B1/CYP24A1/VDR. Renal VD metabolism and serum VD status were unchanged in 0.2 mg/kg Dex-treated rats. However, the higher dose suppressed the three key players involved in VD metabolism but did not alter serum VD levels.

Conclusion: These data provide new evidence that glucocorticoids could affect intracrine actions of VD in the brain and myocardium, which suggests the potential involvement of VD in the neural and cardiac dysfunctions induced by glucocorticoid excess.