Glucocorticoids and cultured human skin cells: specific intracellular binding and structure-activity relationships

Cytosol fractions of both cultured human skin fibroblasts and epidermal keratinocytes contain macromolecules that bind glucocorticoids with high affinity. Using the cytosol of cultured keratinocytes good correlation has been found between the displacement of radiolabelled glucocorticoids (3H-hydrocortisone, 3H-dexamethasone and 3H-triamcinolone acetonide) by a variety of glucocorticoids and the clinical efficacy. The structure-binding relationship studies revealed the relative contribution of various substituents on the steroid molecule for the binding affinity of the steroids. The introduction of a double bond at C1-C2, the presence of 9 alpha-fluoro atom or 11 beta-hydroxy group and the esterification of the 17 alpha-hydroxy group caused an increase, whereas esterification of the hydroxy group on C21 leads to marked decrease of the affinity of the steroid.