Nongenomic steroid action: controversies, questions, and answers

Steroids may exert their action in living cells by several ways: 1). the well-known genomic pathway, involving hormone binding to cytosolic (classic) receptors and subsequent modulation of gene expression followed by protein synthesis. 2). Alternatively, pathways are operating that do not act on the genome, therefore indicating nongenomic action. Although it is comparatively easy to confirm the nongenomic nature of a particular phenomenon observed, e.g., by using inhibitors of transcription or translation, considerable controversy exists about the identity of receptors that mediate these responses. Many different approaches have been employed to answer this question, including pharmacology, knock-out animals, and numerous biochemical studies. Evidence is presented for and against both the participation of classic receptors, or proteins closely related to them, as well as for the involvement of yet poorly understood, novel membrane steroid receptors. In addition, clinical implications for a wide array of nongenomic steroid actions are outlined.