Calcitriol (1,25 di-OH Vitamin D) – 081091

Humans get vitamin D from their normal diet, dietary supplements and from exposure to sunlight.^1-5 Ultraviolet B irradiation of the skin drives the conversion of 7-dehydrocholesterol to previtamin D₃, which is then rapidly converted to vitamin D₃.¹ Vitamin D from the skin and diet is further metabolized in the liver to 25-(OH) vitamin D (or calcidiol).^1-5 Calcidiol is the principle circulating reservoir of vitamin D in plasma and is generally the best indicator of overall vitamin D status. Calcidiol is further converted by the enzyme 25-(OH) D-1α-hydroxylase (CYP27B1) in the proximal tubules of the kidney to the biologically active form of vitamin D, 1,25-(OH)2 vitamin D (or calcitriol).^1-5 The renal production of calcitriol is tightly regulated by plasma parathyroid hormone (PTH)^1-5 and fibroblast growth factor 23 (FGF-23). FGF-23 is a circulating hormone synthesized by osteocytes and osteoblasts.^5-8 Calcitriol and phosphate intake stimulates the synthesis of FGF-23, which, in turn, suppresses calcitriol synthesis and activates calcitriol conversion to inactive metabolites.^1-6

Calcitriol is a steroid-like hormone that binds to a specific cytoplasmic vitamin D receptor (VDR) in the cytoplasm of target cells. The calcitriol-VDR complex then migrates into the nucleus, where its effects are mediated at a transcriptional level.⁵ Renal production of calcitriol is important in the regulation of serum calcium homeostasis and in the maintenance of healthy bone.^1,2,9-11 Calcitriol stimulates the absorption of calcium and phosphate by the intestine and increases calcium and phosphate resorption by the kidney.^1-6,12,13 Calcitriol also suppresses PTH production and regulates osteoblast function and bone resorption.⁵ It has been suggested that calcitriol has roles beyond the calcium-skeletal axis.