SFE2005 Symposia Non classical sites of action of classical hormones (5 abstracts)
A variety of rapid responses to steroid hormones have been identified during the last decade. In contrast to classical actions mediated via nuclear receptors with a time lag of hours, rapid actions occur within seconds or minutes via second messenger signalling cascades. Classical genomic actions are well-defined and sensitive to transcription and protein synthesis inhibitors. Steroid hormones enter the cell by diffusion or via transport proteins and bind to cognate receptors in the cytoplasm. Ligand-bound receptors translocate to the nucleus and regulate target gene expression in a hormone dependent fashion. Non-genomic actions are too rapid to be compatible with RNA and protein synthesis. They can be induced by steroids coupled to membrane-impermeable molecules and also occur in cells that lack nuclei. Rapid actions can be elicited by mutant nuclear receptors that are incapable of binding to DNA and can be identified in nuclear receptor-deficient cells. Thus, it was postulated that rapid actions of steroid hormones could be mediated by membrane receptors unrelated to nuclear receptors, by isoforms of classical receptors that localise to the cell membrane, or by a subpopulation of conventional receptors that associate with membrane signalling complexes. To date three novel membrane proteins have been cloned. The first was an Arabidopsis transmembrane receptor for brassinosteroids with intrinsic serine-threonine kinase activity, the second was a G-protein receptor for progesterone cloned from trout ovary that was found to be a member of a new family of 14 related and conserved G-proteins, and the third was the MAPK-linked integrin alphaVbeta3 that acts as a membrane receptor for thyroid hormone. A large body of evidence has also identified membrane-associated nuclear receptor variants that mediate rapid actions, suggesting that this expanding field will unravel a diverse array of mechanisms by which steroid hormones act at the cell membrane.