125OH2D3

125OH2D3, commonly written as 1,25-dihydroxyvitamin D3 or calcitriol, is the hormonally active metabolite of vitamin D3. It is produced in the kidney by the enzyme 1α-hydroxylase (CYP27B1) from circulating 25-hydroxyvitamin D3 (calcidiol). Its synthesis is tightly regulated by parathyroid hormone (PTH), serum phosphate, and fibroblast growth factor 23 (FGF23); it is also subject to degradation by 24-h-hydroxylase (CYP24A1).

Calcitriol exerts its effects primarily through binding to the vitamin D receptor (VDR), a nuclear receptor that forms a heterodimer with RXR and regulates gene transcription by binding to vitamin D response elements. In the intestine, calcitriol increases calcium and phosphate absorption by upregulating transport proteins such as TRPV6 and calbindin-D9k, and related enzymes. In bone, it modulates remodeling by influencing osteoblast expression of RANKL and osteoprotegerin (OPG), thereby affecting osteoclast activity. Calcitriol also has broader effects on immune function, cell proliferation, and differentiation, and may influence muscle function and cardiovascular processes.

Physiologically, calcitriol helps maintain serum calcium and phosphate homeostasis, supporting bone mineralization and mineral balance. Deficiency can contribute to rickets in children and osteomalacia in adults. Clinically, calcitriol or its analogs are used to treat hypocalcemia and certain forms of kidney disease; excessive levels can cause hypercalcemia and hypercalciuria. Lab assessment often measures 1,25(OH)2D3, though 25(OH)D3 is typically used to gauge vitamin D status, as calcitriol levels can be normal or elevated in some disorders.