The Quaternary Structures of Untransformed Steroid Hormone Receptors: An Open Issue

Oligomeric forms of steroid hormone receptors have been observed since the original detection of these proteins in cytosols from target tissues, and the capacity of receptors to arrange in supramolecular entities was found to be related to their functional untransformed states of low affinity for nuclear acceptor sites. In this paper we discuss the models of quaternary structures of untransformed receptors and steroid-receptor complexes proposed in the last two decades, including homo-oligomers as well as hetero-oligomers containing non-steroid binding proteins and/or RNA. The multiplicity of forms detected in cell-free systems, their stabilization by unphysiological experimental conditions, and their sensitivity to the ionic species employed to prepare and analyze steroid receptors, are critically evaluated, and it is concluded that the extrapolation of models to account for quaternary structure of receptors in intact cells is unwarranted. We have also discussed the experimental strategies which have been developed to circumvent the possible artefactual changes in the arrangements of oligomeric receptors following cell rupture, in order to probe the existence of these forms in vivo, and to characterize their composition and structure. The data obtained by these studies support the concept that oligomeric untransformed steroid receptors exist in intact cells, where they can be present in multiple supramolecular arrangements whose quaternary structures remain to be established.