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


OBJECTIVE
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.


CONCLUSIONS
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.
Institute of Clinical Pharmacy and Pharmacology, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.
Pei
P
Jiang
Ying
Y
Xue
Huan-De
HD
Li
Yi-Ping
YP
Liu
Hua-Lin
HL
Cai
Mi-Mi
MM
Tang
Li-Hong
LH
Zhang
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis; D059445:Anhedonia / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004100:Dihydroxycholecalciferols / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006887:Hydroxycholecalciferols / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming / Q000523:psychology; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase / Q000096:biosynthesis; D014815:Vitamins / Q000378:metabolism*
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D014815:Vitamins; D014807:Vitamin D; D003907:Dexamethasone; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase