The role of the liver in vitamin D metabolism

Abstract

Vitamin D₃is generated in the skin, and subsequently metabolized to 25OHD₃in the liver and then to 1α,25(OH)2D₃in the kidney, and thereafter, 1α,25(OH)₂D₃exerts its biological functions by regulating gene transcription via binding to nuclear receptor, VDR in target cells. 1α,25(OH)₂D₃plays a critical role in this vitamin D endocrine system. However, it has become obvious in the recent years that plasma concentrations of 25OHD₃but not 1α,25(OH)₂D₃, significantly associate with the incident risk of life style-related diseases such as osteoporosis and diabetes. Moreover, it appears that 25OHD₃itself acts as a ligand for VDR. Based on the findings that liver is not only the major productive organ for 25OHD₃but also the sole productive organ for DBP which serves to deliver 25OHD₃to tissues and stores 25OHD₃in the blood circulation, it is believed that liver plays important roles in vitamin D metabolism and vitamin D functions. The roles of the liver in vitamin D metabolism including the regulatory mechanism of the expression and activation of a 25OHD₃biosynthetic enzyme, CYP2R1, remain largely unsolved.