Differences in selectivity of inhaled glucocorticoids (IGCs) to the glucocorticoid receptors (GR)

Abstract Rationale Newer inhaled glucocorticoids are characterized by very high receptor binding affinities to the glucocorticoid receptor. As potential side effects might be also related to binding of these compounds to other steroid receptor, we compare here the binding affinities of a number of inhaled glucocorticoids to both the glucocorticoid (GR) and progesterone receptor (PR). Methods The competitive binding assays were conducted in the cytosol of rat lung and sheep uterus using selective radioligands for both receptors. The ratios of relative binding affinities (RBA PR /RBA GR ) were used to describe the selectivity (with higher ratios indicating the lowest selectivity). Results Mometasone furoate (MF) showed the lowest GR selectivity (PR/GR ratio of 0.878) while the higher selectivity of the other glucocorticoids tested was indicated by selectivity ratios ranging from 0.022 to 0.1 (mometasone: 0.022, budesonide: 0.022, triamcinolone acetonide: 0.035, fluticasone propionate: 0.084, beclomethasone monopropionate: 0.11). The relatively high selectivity for mometasone (lacking the 17-furoate ester) clearly indicates that the interaction of 17β furoate moiety in mometasone furoate is responsible for the high affinity towards the progesterone receptor. Conclusion The study shows that there are differences in selectivity among various steroids tested to GR, and that mometasone furoate is the least specific glucocorticoid investigated.