Nongenomic effects of 17beta-estradiol--diversity of membrane binding sites

The classical model of the action of 17beta-estradiol comprises binding of this gonadal steroid hormone to nuclear estrogen receptors leading to the modulation of gene transcription and protein synthesis. However, in the last few years several evidences about the rapid nongenomic action of 17beta-estradiol via the stimulation of putative receptors located in the cell membrane have also been reported. These nongenomic responses occur within a few minutes and are insensitive to the inhibitors of transcription and translation; however, no such membrane receptors have been cloned so far. In this review article, we present a survey showing that such membrane binding sites of 17beta-estradiol have rather different ligand specificity properties than that of classical genomic estrogen receptors concerning the potential activity of different estrogens and other steroid hormones, supporting the conception of structurally distinct receptors for genomic and nongenomic pathways. The fact that rapid responses to 17beta-estradiol could be induced by a wide concentration range from some picomolar to high micromolar doses points to the diversity of these nongenomic membrane binding sites as well as the complexity of their functioning.