NONGENOMIC ACTIONS OF THE STEROID-HORMONE 1-ALPHA,25-DIHYDROXYVITAMIN D-3

Recent studies indicate that the vitamin D hormone, 1 alpha, 25-dihydroxyvitamin D-3 exerts rapid effects (seconds to minutes) in a variety of cell types. These rapid nongenomic actions in osteoblasts include effects on membrane voltage-gated calcium channels, phospholipase C activity, and the sodium/hydrogen antiport. Since the rapid effects occur in osteoblasts that lack the nuclear vitamin D receptor, it is postulated that the nongenomic responses to the hormone reflect interaction with a separate, membrane localized signalling system. Preliminary studies demonstrate the presence of a receptor on the membranes of osteoblasts that lack the nuclear vitamin D receptor. This membrane receptor recognizes 1 alpha,25-dihydroxyvitamin D-3 and its inaction 1 beta epimer, but not 25-hydroxyvitamin D-3. These rapid nongenomic actions generated by interaction with the membrane receptor modulate the effects of the hormone on gene transcription. Thus, the rapid nongenomic pathway may play a regulatory function in modulating the genomic pathways affected by 1 alpha,25-dihydroxyvitamin D-3. (C) 1994 Wiley-Liss, Inc.