Corticosteroid-calcium complexes

Glucocorticoids and calcium ions are shown to interact to yield a complex with properties that are distinct from those of the reactants. Reaction of steroids with Ca2+ appears to require the dihydroxyacetone side chain, since other structures do not react. Evidence for complex formation are: increased aqueous solubility of cortisol when Ca2+ is added to an aqueous or a biphasic aqueous/chloroform (or ethyl acetate) system; increased rate of migration of cortisol during reversed-phase thin-layer chromatography and HPLC; chromatographic comigration of 45Ca2+ and 3H-labeled cortisol; coprecipitation of 45Ca2+-3H-cortisol complexes. After dissociation of the cortisol-calcium complex, the only steroid recovered was cortisol. By the above criteria, the properties of cortisol were not affected by Sr2+, Ba2+, or Mg2+. The cleavage patterns of cortisol in the mass spectrometer corresponded to that of 11 beta-hydroxyandrostenedione when Ca2+ was present, and to cortisol in its absence. We therefore postulate that the structure of the dihydroxyacetone side chain was transiently altered by Ca2+, resulting in a labile C17-C20 bond. These results support our earlier proposal that the chemical and physico-chemical properties of corticosteroids are modified by calcium ions.