Vitamin D and its receptor during late development

Abstract

Expression of the vitamin D receptor (VDR) is widespread but may vary depending on the developmental stage of the animal, and therefore may differentially influence phenotypic function. Thus, the major role of the 1,25-dihydroxyvitamin D [1,25(OH)2D]/VDR system is to regulate mineral and skeletal homeostasis, although mainly after birth. Post-natally, under conditions of low dietary calcium, the 1,25(OH)2D/VDR system enhances intestinal transcellular transport of calcium and possibly paracellular calcium entry by regulating genes that are critical for these functions. This process, by providing adequate calcium, is essential for normal development of the skeletal growth plate and mineralization of bone. Furthermore, blood calcium and phosphorus homeostasis is maintained by an interplay between feedback loops of the 1,25(OH)2D/VDR system with parathyroid hormone and with fibroblast-growth factor (FGF) 23 respectively. The 1,25(OH)2D/VDR system can also modulate the expression of genes involved in both bone formation and resorption post-natally. Ligand independent activity of the VDR normally influences mammalian hair cycling after birth by potentiating Wnt and bone morphogenetic protein (BMP) signaling. Nevertheless ligand bound VDR may also modulate epidermal cell proliferation/differentiation by regulating the balance in function of c-MYC and its antagonist the transcriptional repressor MAD1/MXD1 in skin epithelia. The 1,25(OH)2D/VDR system can also modulate innate immune cells and promote a more tolerogenic immunological status and may therefore influence inflammation and the development of autoimmunity; whether this impacts the fetus is uncertain. This article is part of a Special Issue entitled: Nuclear receptors in animal development.