Recent studies indicate that the vitamin D hormone, 1α,25-Dohydroxyvitamin D 3 exerts rapid effects (seconds to minutes) in a variety of cell types. These rapid nongenomic actions in osteoblasts include effects on membrance voltage-gated calcium chananels, phosphlipase C activity, and the sodium/dydrogen antiport. Since the rapid effects occur in osteoblasts that lack the neclear 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 neclear vitamin D. This membranes receptors recognizes 1 a, 25-dihyrooxyvitamin D 3 and its inaction 1β epimer, but not 25-hydrovitamin D 3 . These rapid nongenomic actions generated by interaction with the membrane receptor modulate the effect of the hormone on gene transcription. Thus, the rapid nongenomic pathway may play a regulatory function in modulating the genomic pathways affected by 1 a 25-dihydroxyvitamin D 3 .
Steroid hormones classically mediate their actions by binding to intracellular receptor proteins that migrate to the nucleus and act as transcription factors to change gene expression. However, evidence is now accumulating for rapid, non-genomic effects of steroids. There is considerable controversy over the mechanisms underlying such effects. In a number of cases evidence has been presented for the direct activation of G-protein coupled receptors (GPCRs) by steroids, either at the plasma membrane, or at intracellular locations. Here, we will focus on the non-genomic actions of ecdysteroids on a Drosophila GPCR, DopEcR (CG18314), which can be activated by both ecdysone and the catecholamine, dopamine. We will also point out parallels between this system and the activation of the vertebrate GPCR, GPER1 (GPR30), which is thought to be activated by 17β-estradiol. We propose that the cellular localization and signalling properties of both DopEcR and GPER1 may be cell specific and depend upon their interactions with both accessory molecules and signalling pathways.