title: Aldosterone and mineralocorticoid receptors: orphan questions.
abstract: Classically, mineralocorticoid receptors (MR) are activated by aldosterone to promote unidirectional transepithelial sodium transport. Activation of MR in nonepithelial tissues has been shown to elevate blood pressure (central nervous system; CNS) and to cause hypertrophy and fibrosis (heart). For both epithelial and nonepithelial tissues, there remain a variety of questions regarding MR which are not only unanswered but also essentially not addressed. Seven such questions include: (1) how the physiologic glucocorticoids (cortisol and corticosterone) can mimic aldosterone action in epithelial MR, but act as antagonists in the heart and AV3V region; (2) how salt facilitates the nonepithelial, pathophysiologic effects of aldosterone; (3) how aldosterone activates unprotected AV3V MR in the face of orders of magnitude higher circulating glucocorticoid concentrations; (4) how unprotected nonepithelial MR act as "always occupied" receptors in guinea pigs and other species; (5) how, when 11beta hydroxysteroid dehydrogenase type 2 is active, epithelial MR occupied by physiologic glucocorticoids appear transcriptionally inactive; (6) how aldosterone activates epithelial MR in the face of approximately 103-fold higher glucocorticoid levels, plasma binding and 11beta hydroxysteroid dehydrogenase type 2 activity notwithstanding; and (7) how aldosterone produces changes in urinary [K+] before [Na+].
authors.affiliation: Baker Medical Research Institute, Melbourne, Australia. sue.smith@baker.edu.au
authors.forename: J W
authors.initials: JW
authors.lastname: Funder
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000502:physiology; D000818:Animals; D003345:Corticosterone / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism; D006854:Hydrocortisone / Q000502:physiology; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D005938:Glucocorticoids; D018161:Receptors, Mineralocorticoid; D012965:Sodium Chloride; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003345:Corticosterone; D006854:Hydrocortisone