Premium
Specific hydroxylations determine selective corticosteroid recognition by human glucocorticoid and mineralocorticoid receptors
Author(s) -
Hellal-Levy Chantal,
Couette Brigitte,
Fagart Jérôme,
Souque Anny,
Gomez-Sanchez Celso,
Rafestin-Oblin Marie-Edith
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01667-1
Subject(s) - transactivation , mineralocorticoid receptor , mineralocorticoid , glucocorticoid receptor , aldosterone , receptor , glucocorticoid , endocrinology , steroid hormone , steroid , hormone , medicine , chemistry , biology , biochemistry , transcription factor , gene
The ligand binding domains of the human mineralocorticoid receptor (hMR) and glucocorticoid receptor (hGR) display a high sequence homology. Aldosterone and cortisol, the major mineralocorticoid and glucocorticoid hormones, are very closely related, leading to the cross‐binding of these hormones to both receptors. The present study reports on the mechanism by which hMR and hGR are activated preferentially by their cognate hormones. We found that the ability of corticosteroids to stimulate the receptor's transactivation function is depending on the stability of the steroid‐receptor complexes. In the light of a hMR structural model we propose that contacts through the corticosteroid C21 hydroxyl group are sufficient to stabilize hMR but not hGR and that additional contacts through the C11‐ and C17‐hydroxyl groups are required for hGR.