[Membrane localization of the nuclear receptor: a paradox with important consequences]

Lipophilic signal compounds can exert regulatory effects in a cell at the level of gene expression via interactions with cognate nuclear receptors that function as transcriptional factors, and also by rapid regulation of activities of proteins participating in intracellular transduction of extracellular signals. This nongenomic way can be mediated by translocation of a subset of nuclear receptors to cell membrane. By the example of estrogen receptors, mechanisms of such translocation and ligand-induced coupling between receptors and effector proteins of cell membrane are reviewed. Both immediate physiological reactions and delayed effects which are secondary, at the transcriptional level can be the consequences of such nongenomic action. The revealing of nuclear receptors in cell membrane adds to understanding of mechanisms of various regulatory stimuli integration by a cell, and is an important step towards design of selective hormonal analogs.