The interaction of nivazol with the glucocorticoid receptor from rat and rhesus monkey target tissues.
Steroid hormone receptor competition techniques were used to evaluate the glucocorticoid receptor binding properties of nivazol and its 11 beta-hydroxy derivative, Win 44577 in rat and monkey target tissues. These agents competitively inhibited the binding of 3H-dexamethasone to the glucocorticoid receptor from the liver and anterior pituitary from both rat and monkey with relative binding affinities of Win 44577 greater than dexamethasone greater than nivazol greater than cortisol in all cases. However, nivazol and Win 44577 had approximately twice the affinity for the anterior pituitary glucocorticoid receptor from both species. Neither compound demonstrated any significant binding to rat estrogen, progestin or androgen receptors. These results are consistent with a glucocorticoid receptor mediated mechanism of action for nivazol and Win 44577; however, the difference in the endocrine profile of nivazol in the rhesus monkey versus the rat does not appear to be due to a species selectivity in the affinity of nivazol for the glucocorticoid receptor from central or peripheral target tissue.
D000818:Animals; D001667:Binding, Competitive; D003907:Dexamethasone / Q000378:metabolism; D005260:Female; D006854:Hydrocortisone / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011244:Pregnadienediols / Q000378:metabolism; D011245:Pregnadienes / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013045:Species Specificity
D011244:Pregnadienediols; D011245:Pregnadienes; D011965:Receptors, Glucocorticoid; C041704:nivazol; D003907:Dexamethasone; C046882:Win 44577; D006854:Hydrocortisone