title: Genomic and rapid effects of aldosterone: what we know and do not know thus far.
abstract: Aldosterone is the most known mineralocorticoid hormone synthesized by the adrenal cortex. The genomic pathway displayed by aldosterone is attributed to the mineralocorticoid receptor (MR) signaling. Even though the rapid effects displayed by aldosterone are long known, our knowledge regarding the receptor responsible for such event is still poor. It is intense that the debate whether the MR or another receptor-the "unknown receptor"-is the receptor responsible for the rapid effects of aldosterone. Recently, G protein-coupled estrogen receptor-1 (GPER-1) was elegantly shown to mediate some aldosterone-induced rapid effects in several tissues, a fact that strongly places GPER-1 as the unknown receptor. It has also been suggested that angiotensin receptor type 1 (AT1) also participates in the aldosterone-induced rapid effects. Despite this open question, the relevance of the beneficial effects of aldosterone is clear in the kidneys, colon, and CNS as aldosterone controls the important water reabsorption process; on the other hand, detrimental effects displayed by aldosterone have been reported in the cardiovascular system and in the kidneys. In this line, the MR antagonists are well-known drugs that display beneficial effects in patients with heart failure and hypertension; it has been proposed that MR antagonists could also play an important role in vascular disease, obesity, obesity-related hypertension, and metabolic syndrome. Taken altogether, our goal here was to (1) bring a historical perspective of both genomic and rapid effects of aldosterone in several tissues, and the receptors and signaling pathways involved in such processes; and (2) critically address the controversial points within the literature as regarding which receptor participates in the rapid pathway display by aldosterone.
authors.affiliation: Laboratory of Hypertension, Research Center in Biological Science, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil.
authors.forename: Milla Marques
authors.initials: MM
authors.lastname: Hermidorff
authors.affiliation: Laboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Leonardo Vinícius Monteiro
authors.initials: LV
authors.lastname: de Assis
authors.affiliation: Laboratory of Hypertension, Research Center in Biological Science, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil. mauroisoldi@hotmail.com.
authors.forename: Mauro César
authors.initials: MC
authors.lastname: Isoldi
mesh_terms: D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D023281:Genomics / Q000379:methods*; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D012313:RNA / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C109584:GPER1 protein, human; D000451:Mineralocorticoid Receptor Antagonists; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D012313:RNA
keywords: Aldosterone; G protein-coupled estrogen receptor-1 (GPER-1); Genomic effects; Mineralocorticoid receptor (MR); Rapid or non-genomic effect