Determinants of specificity of transactivation by the mineralocorticoid or glucocorticoid receptor

Endocrinology
S S Lim-TioP J Fuller

Abstract

Glucocorticoids and mineralocorticoids have distinct in vivo roles despite close structural homology and similarities in vitro. Known mechanisms of specificity focus on factors extrinsic to the receptor; interactions that directly regulate the receptor to confer specificity are less well understood, particularly for the mineralocorticoid receptor (MR). To examine relative MR vs. glucocorticoid receptor (GR) function in a more physiological context, we compared transactivation by GR and MR in the standard experimental fibroblast CV-1 cell line, the renal epithelial LLC-PK1 line, and neuronal medullary raphe RN33B cells. Maximal transactivational activity mediated by MR, relative to that mediated by GR, is enhanced in both of these cell lines and is primarily conferred by an N-terminal-mediated enhancement of the MR response. In addition, the ligand concentration required for maximal transcriptional activity of the GR varies significantly between cell lines. This is independent of binding affinity or 11beta-hydroxysteroid dehydrogenase-mediated inactivation and may contribute to in vivo tissue-specific differences in responses to the GR. Although ligand binding affinity is clearly conferred by the LBD, receptor-specific variation...Continue Reading

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Citations

Apr 12, 2000·Kidney International·P J FullerF E Brennan
Sep 9, 2008·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·P HeiserH Vedder
Jul 22, 2004·Annals of the New York Academy of Sciences·Evangelia CharmandariGeorge P Chrousos
Nov 21, 2009·Experimental Dermatology·Nicolette FarmanRalf Paus
Aug 8, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Kaori OkaYoshinao Katsu
Apr 8, 2015·Clinical Otolaryngology : Official Journal of ENT-UK ; Official Journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery·A F Goodall, M A Siddiq
Feb 8, 2005·Journal of the Society for Gynecologic Investigation·Maureen Keller-WoodDaying Zhang
Jul 30, 2002·Molecular Endocrinology·Matthew R Yudt, John A Cidlowski
Feb 26, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Monika Proszkowiec-Weglarz, Tom E Porter
Jun 10, 2020·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Sayoko Ito-HarashimaTakashi Yagi
Jul 5, 2003·Physiological Reviews·Ralf M LoselMartin Wehling
Feb 24, 2001·American Journal of Physiology. Renal Physiology·N Farman, M E Rafestin-Oblin
Apr 12, 2016·Journal of Animal Science·C R Ralph, A J Tilbrook
Jun 18, 2003·The Journal of Biological Chemistry·Tsunenori KodamaHirotoshi Tanaka
Dec 14, 1999·The Journal of Biological Chemistry·F M RogersonP J Fuller
Aug 9, 2019·Experimental Eye Research·Jérémie CanonicaFrancine Behar-Cohen
Dec 3, 1999·Biochemical and Biophysical Research Communications·V KollaG Litwack

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