Specific hydroxylations determine selective corticosteroid recognition by human glucocorticoid and mineralocorticoid receptors

FEBS Letters

Hellal-Levy, Chantal¹  Couette, Brigitte¹  Souque, Anny¹  Gomez-Sanchez, Celso³  Fagart, Jérôme²  Rafestin-Oblin, Marie-Edith¹ 

[1] INSERM U478, Faculté de Médecine Xavier Bichat, Institut Fédératif de Recherche 02, 16 rue Henri Huchard, P.O. Box 416, 75780 Paris Cedex 18, France;IGBMC, 1 rue Laurent Fries, P.O. Box 163, 67404 Illkirch Cedex, France;Harry S. Truman Memorial Veterans Hospital and Cosmopolitan International Diabetes Center, University of Missouri-Columbia, Columbia, MO, USA

关键词: Aldosterone;    Cortisol;    Mineralocorticoid;    Glucocorticoid;    Steroid receptor;   

DOI  :  10.1016/S0014-5793(99)01667-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown