Nongenomic actions of steroids--from the laboratory to clinical implications.

Abstract

In the classical concept of steroid action, steroids bind to cytoplasmic receptors and modulate nuclear transcription after translocation of steroid-receptor complexes into the nucleus. Due to similarities of molecular structure, receptors for steroids, retinoids, vitamin D3 and thyroid hormone are considered to represent a superfamily of receptors. While genomic steroid effects been evident for several decades, rapid effects of steroids have been characterized only recently. These rapid actions are likely to be transmitted by specific membrane receptors. Binding sites in membranes have been characterized which display binding features compatible with an involvement in rapid steroid signaling. Characteristics of putative membrane receptors are completely distinct from those of intracellular steroid receptors, a fact which is further supported by the inability of classic steroid receptor antagonists to suppress nongenomic steroid actions. The cloning and functional expression of a putative progesterone membrane receptor has been achieved. Drugs that specifically modulate nongenomic action alone or even both genomic and nongenomic actions may be applied in various areas such as the cardiovascular and central nervous systems, and treatment of infertility and electrolyte homeostasis.