[Vitamin D: biosynthesis, metabolism and mechanism of action at the cellular level].

Abstract

The term vitamin D includes various chemical species. Vitamin D3 a true endogenous or alimentary prohormone is converted into its main metabolite, calcitriol, by successive hydroxylations in the liver in position 25 and in the kidney in position 1, the production of which is controlled by several factors including parathyroid hormone, blood calcium and phosphorus or insulin as well as by the metabolites of the hormone itself. It controls the synthesis of numerous peptides by acting on gene expression. Indeed, several structural proteins are involved including procollagen alpha 1l, core protein of proteoglycans, diverse regulatory peptides such as protooncogene c-myc and growth factors, "Tumor Necrosis Factor or TNF" and "Nerve Growth Factor or NGF" or hormones such as parathyroid hormone, and finally constitutive proteins of the mineralized tissues such as osteonectin, osteocalcin, osteopontin and calbindins. Therefore, it modulates very different cellular processes. It acts via a nuclear receptor the structure and function of which have been investigated by genetic engineering (cloning of genes encoding for the receptor and hormono-dependent peptides, transfection assays, directed mutagenesis). Actual studies investigate its role in the formation of the complex for transcription initiation near ADN sites, the "Vitamin D Responsive Element or VDRE", located upstream vitamin D-responsive genes and approximately RNA polymerase II. The receptor, which is present in many cell types at various concentrations, would determine spatial and temporal patterns of calcitriol action during development in conjunction with chromatin factors.