Multiple actions of steroid hormones--a focus on rapid, nongenomic effects.
According to the traditional model, steroid hormones bind to intracellular receptors and subsequently modulate transcription and protein synthesis, thus triggering genomic events finally responsible for delayed effects. Based upon similarities in molecular structure, specific receptors for steroids, vitamin D(3) derivatives, thyroid hormone, retinoids, and a variety of orphan receptors are considered to represent a superfamily of steroid receptors. In addition, very rapid effects of steroids mainly affecting intracellular signaling have been widely recognized that are clearly incompatible with the genomic model. These rapid, nongenomic steroid actions are likely to be transmitted via specific membrane receptors. Evidence for nongenomic steroid effects and distinct receptors involved is presented for all steroid groups including related compounds like vitamin D(3) and thyroid hormones. The physiological and clinical relevance of these rapid effects is still largely unclear, but their existence in vivo has been clearly shown in various settings including human studies. Drugs that specifically affect nongenomic steroid action may find applications in various clinical areas such as cardiovascular and central nervous disorders, electrolyte homeostasis, and infertility. In addition to a short description of genomic steroid action, this review pays particular attention to the current knowledge and important results on the mechanisms of nongenomic steroid action. The modes of action are discussed in relation to their potential physiological or pathophysiological relevance and with regard to a cross-talk between genomic and nongenomic responses.
Falkenstein
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Institute of Clinical Pharmacology, Faculty for Clinical Medicine at Mannheim, University of Heidelberg, Mannheim, Germany.
Tillmann
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HC
Christ
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Feuring
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Wehling
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D000818:Animals; D002762:Cholecalciferol / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D006801:Humans; D008901:Mineralocorticoids / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology; D011987:Receptors, Steroid / Q000502:physiology; D020218:Response Elements; D013256:Steroids / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology
D005938:Glucocorticoids; D012739:Gonadal Steroid Hormones; D008901:Mineralocorticoids; D011987:Receptors, Steroid; D013256:Steroids; C018370:pregnenolone sulfate; D014284:Triiodothyronine; D002762:Cholecalciferol; D011284:Pregnenolone