1,25(OH)2-vitamin D3 induces translocation of the vitamin D receptor (VDR) to the plasma membrane in skeletal muscle cells

Abstract

1,25-dihydroxy-vitamin D3 (1,25(OH)2D3), the hormonally active form of vitamin D3, acts through two different mechanisms. In addition to regulating gene expression via the specific intracellular vitamin D receptor (VDR), 1,25(OH)2D3 induces rapid, non-transcriptional responses involving stimulation of transmembrane signal transduction pathways. The activation of second messengers supports the hypothesis that a membrane-bound steroid receptor similar to those that mediate peptide hormone biology exists. Skeletal muscle is a target tissue for 1,25(OH)2D3. Avian embryonic skeletal muscle cells (myoblasts/myotubes) have been shown to respond both genomically and non-genomically to the hormone. The present study provides evidence indicating that short-term treatment (1-10 min) with 1,25(OH)2D3 induces translocation of the VDR from the nuclear to the microsomal fraction in chick myoblasts. This translocation is blocked by colchicine, genistein, or herbimycin, suggesting the involvement of microtubular transport and tyrosine kinase/s in the relocation of the receptor. By isolation of plasma membranes, it was demonstrated that the hormone increases the amounts of VDR specifically in this fraction. These results suggest that the nuclear VDR may be the receptor that mediates the non-genomic effects of 1,25(OH)2D3 in chick myoblasts. © 2002 Wiley-Liss, Inc.