Thyroid hormones decrease plasma 1α,25-dihydroxyvitamin D levels through transcriptional repression of the renal 25-hydroxyvitamin D3 1α-hydroxylase gene (CYP27B1).

The primary determinant of circulating 1α,25-dihydroxyvitamin D (1,25[OH]2D) levels is the activity of 25-hydroxyvitamin D-1α-hydroxylase (cytochrome P450 27B1 [CYP27B1]) in the kidney. Hyperthyroid patients have been reported to have low levels of plasma 1,25(OH)2D. However, the detailed mechanism of thyroid hormone action on vitamin D metabolism is still poorly understood. The present study determined whether renal CYP27B1 gene expression was negatively regulated by thyroid hormones. T3-induced hyperthyroid mice showed marked decreases in plasma 1,25(OH)2D levels and in renal expression of CYP27B1 mRNA but no changes in plasma concentrations of calcium, PTH, or fibroblast growth factor-23. In addition, we observed that T3 administration significantly decreased plasma 1,25(OH)2D and renal CYP27B1 mRNA levels that were increased by low-calcium or low-phosphorus diets and induced hypocalcemia in mice fed a low-calcium diet. Promoter analysis revealed that T3 decreases the basal transcriptional activity of ...