Aldosterone and mineralocorticoid receptors: orphan questions

Kidney Int. 2000 Apr;57(4):1358-63. doi: 10.1046/j.1523-1755.2000.00975.x.


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+].

Publication types

  • Review

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases
  • Aldosterone / physiology
  • Animals
  • Corticosterone / physiology
  • Glucocorticoids / metabolism
  • Hydrocortisone / physiology
  • Hydroxysteroid Dehydrogenases / metabolism
  • Receptors, Mineralocorticoid / physiology*
  • Sodium Chloride / pharmacology


  • Glucocorticoids
  • Receptors, Mineralocorticoid
  • Sodium Chloride
  • Aldosterone
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Corticosterone
  • Hydrocortisone