Non-genomic steroid hormone effects: membrane or intracellular receptors?

A controversy regarding the identity of receptors that mediate nongenomic, transcription-independent cellular responses to steroids is presently attracting considerable scientific interest. While there is strong evidence for classic receptors belonging to the nuclear receptor superfamily to mediate nongenomic steroid effects in some cases, it does not exist for others. Nongenomic estrogen effects seem to predominantly involve classical estrogen receptors, both residing in cytoplasm and at the cell membrane. On the other hand, there is increasing evidence for the existence of nonrelated membrane receptors for estrogens, mediating CNS effects. Novel membrane receptors for other steroids have been recently cloned, with the demonstration of their biological relevance still largely pending. Recent findings on new and unexpected properties of classic receptors have partially deflected the interest from novel, nonclassic membrane receptors, which are being progressively identified at present. In addition, new findings pose challenges to some of the conclusions drawn from earlier experiments, and potential involvement of receptors and mechanisms of action need to be reconsidered. To know the nature of receptors involved will be key to beneficial medical translation of specific and targeted steroid responses. Differential pharmacological exploitation of different steroid receptors seems to become a tangible option.