title: Corticosteroid receptors, 11 beta-hydroxysteroid dehydrogenase, and the heart.
abstract: Mineralocorticoid and glucocorticoid hormones are known as corticosteroid hormones and are synthesized mainly in the adrenal cortex; however, more recently the enzymes involved in their synthesis have been found in a variety of cells and tissues, including the heart. The effects of these hormones are mediated via both cytoplasmic mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs), which act as ligand-inducible transcription factors. In addition, rapid, nongenomically mediated effects of these steroids can occur that may be via novel corticosteroid receptors. The lipophilic nature of these hormones allows them to pass freely through the cell membrane, although the intracellular concentration of mineralocorticoids and glucocorticoids is dependent on several cellular factors. The main regulators of intracellular glucocorticoid levels are 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) isoforms. 11 beta HSD1 acts predominantly as a reductase in vivo, facilitating glucocorticoid action by converting circulating receptor-inactive 11-ketoglucocorticoids to active glucocorticoids. In contrast, 11 beta HSD 2 acts exclusively as an 11 beta-dehydrogenase and decreases intracellular glucocorticoids by converting them to their receptor-inactive 11-ketometabolites. Furthermore, P-glycoproteins, by actively pumping steroids out of cells, can selectively decrease steroids and local steroid synthesis can increase steroid concentrations. Receptor concentration, receptor modification, and receptor-protein interactions can also significantly impact on the corticosteroid response. This review details the receptors and possible mechanisms involved in both mediating and modulating corticosteroid responses. In addition, direct effects of corticosteroids on the heart are described including a discussion of the corticosteroid receptors and the mechanisms involved in mediating their effects.
authors.affiliation: Molecular Physiology Laboratory, Baker Heart Research Institute, Melbourne 8008, Victoria, Australia.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Sheppard
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D001665:Binding Sites; D006332:Cardiomegaly; D003345:Corticosterone / Q000096:biosynthesis; D015870:Gene Expression; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction; D009206:Myocardium / Q000378:metabolism; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
chemical_list: D000305:Adrenal Cortex Hormones; D007473:Ion Channels; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003345:Corticosterone