Nongenomic Steroid Action: Controversies, Questions, and Answers

Abstract

Lösel, Ralf M., Elisabeth Falkenstein, Martin Feuring, Armin Schultz, Hanns-Christian Tillmann, Karin Rossol-Haseroth, and Martin Wehling. Nongenomic Steroid Action: Controversies, Questions, and Answers. Physiol Rev 83: 965–1016, 2003; 10.1152/physrev.00003.2003.—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.

Nutritional flavonoids impact on nuclear and extranuclear estrogen receptor activities

“…The mechanism by which E2 exerts proliferative properties has been assumed to be exclusively mediated by ERα-induced rapid membrane-starting actions (Marino et al, 1998;Castoria et al, 1999;Lobenhofer et al, 2000;Marino et al, 2001;Castoria et al, 2001;Marino et al, 2002;Marino et al, 2003;Acconcia et al, 2005b), whereas E2 induces cell death through ERβ nongenomic signaling (Acconcia et al, 2005b). In the nervous system, E2 influences neural functions (e.g., cognition, behavior, stress responses, and reproduction) in part inducing such rapid responses (Farach-Carson and Davis, 2003;Losel et al, 2003). In the liver, rapid E2-induced signals are deeply linked to the expression of LDL-receptor and to the decreased cholesterol-LDL levels in the plasma (Marino et al, 2001;Distefano et al, 2002).…”

17‐β‐Estradiol activates maxi‐K channels through a non‐genomic pathway in human breast cancer cells

“…These observations permitted the proposition of an alternative (non-genomic) pathway that would be responsible, at least in part, for the cellular activation following steroid stimulation [4][5][6]. Various alternative effects of steroids have been reported including the activation of membrane receptors, the modulation of ion channels or effects such as the regulation of gene transcription secondary to the activation of signalling cascades (e.g., cAMP or MAP-Kinase cascades) [7].…”

Effects of Aldosterone on the Vasculature

“…7,8 In addition to its classical genomic mechanisms, aldosterone exerts effects through rapid nongenomic pathways that may also be important in hypertension. 9 Some studies suggest that aldosterone influences vascular contraction, as discussed below. Furthermore, aldosterone modulates membrane receptors and signaling molecules and influences the actions of a variety of agents to sensitize the vasculature to effects of various agents that induce vasoconstriction or result in direct effects on growth and remodeling.…”