Abstract
The differential sensitivity of the rat liver glucocorticoid receptor (GR) to sulfhydryl group modifying agents when bound to various agonist and antagonist ligands was studied. [ 3H]Triamcinolone acetonide (TA) binding was completely abolished by previous treatment of the unbound receptor with various N-alkylmaleimides. On the contrary, [ 3H]RU486 binding was only slightly affected by treatment with N-ethylmaleimide (NEM) and more significantly decreased with maleimides bearing bulky substituents. Ligand exchange experiments demonstrated that, unlike the agonist TA, the antiglucocorticoid RU486 was unable to protect the GR binding site from the effect of NEM. This lack of protection would seem to be due to the presence of the bulky 11β-substituent in RU486 since RU26988 and RU28362, two 11β hydroxylated glucocorticoids bearing the same 17α-propynyl side chain as RU486 but lacking the 11β-substituent could protect GR against NEM. The ability of a GR ligand to prevent NEM inactivation of TA binding appeared unrelated to its agonist or antagonist nature: deacylcortivazol, a potent agonist, afforded no protection whereas antagonists of the 17β-carboxamide series did. These data strongly suggest that compounds bearing bulky substituents on the steroid A and/or C rings, like deacylcortivazol and RU486, are positioned differently from canonical glucocorticoids in the steroid binding groove of the GR.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Journal of Steroid Biochemistry and Molecular Biology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.