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Multiple aspects of mineralocorticoid selectivity.

N Farman1, M E Rafestin-Oblin

  • 1Institut National de la Santé et de la Recherche Médicale U-478, Faculté de Médecine X. Bichat-Institut Fédératif de Recherches 02, 75870 Paris Cedex 18, France. farman@bichat.inserm.fr

American Journal of Physiology. Renal Physiology
|February 24, 2001
PubMed
Summary

Aldosterone

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Renal Physiology

Background:

  • Aldosterone is key for renal sodium reabsorption via the mineralocorticoid receptor (MR).
  • Glucocorticoid receptor (GR) is co-expressed with MR, potentially influencing aldosterone target cells.
  • Steroids can bind both MR and GR, with MR having equal affinity for aldosterone and glucocorticoids.

Purpose of the Study:

  • To explore mechanisms enabling specific aldosterone effects despite high glucocorticoid levels.
  • To understand how MR and GR interactions fine-tune cellular functions.
  • To investigate alterations in these interactions in pathophysiological conditions.

Main Methods:

  • Review of cellular and molecular mechanisms governing corticosteroid receptor function.
  • Analysis of enzyme activity (11beta-hydroxysteroid dehydrogenase) in glucocorticoid metabolism.
  • Examination of receptor dimerization and transcription factor interactions.

Main Results:

  • Local metabolism inactivates glucocorticoids, aiding aldosterone specificity.
  • Intrinsic MR properties and differential ligand contacts contribute to selectivity.
  • MR/GR dimerization and interactions with transcription factors modulate cellular responses.

Conclusions:

  • Multiple mechanisms ensure aldosterone-specific regulation in target cells.
  • Cellular responses are fine-tuned by corticosteroid cooperation and tissue-specific factors.
  • Dysregulation of these interactions can occur in disease states.

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