Formation of covalent adducts between cortisol and 16 alpha-hydroxyestrone and protein: possible role in the pathogenesis of cortisol toxicity and systemic lupus erythematosus.

Publisher Website
Google Scholar
Abstract
The incubation of [human] albumin with cortisol or 16.alpha.-hydroxyestrone results in the formation of covalent steroid-protein adducts. The rate of adduct formation increases in the presence of sodium cyanoborohydride (NaCNBH3), indicating that the reaction proceeds nonenzymatically through a Schiff base intermediate. Under nonreducing conditions, a stable adduct forms with cortisol and 16.alpha.-hydroxyestrone, but not with estrone, which lacks a hydroxyl group adjacent to the reactive carbonyl. A Heyns rearrangement involving the adjacent hydroxyl group may trap the Schiff base and produce a stable ketoamine adduct. The binding of 16.alpha.-hydroxyestrone and cortisol to albumin is significantly inhibited by acetylsalicyclic acid, which acetylates an .epsilon.-amino group of a lysine residue in albumin. High-pressure liquid chromatography analysis of an acid hydrolysate of 16.alpha.-hydroxyestrone-albumin shows that a product containing 16.alpha.-hydroxyestrone coelutes with a standard prepared by reacting 16.alpha.-hydroxyestrone with the .epsilon.-amino group of lysine. Evidently, the formation of covalent steroid-protein adducts is a generalized phenomenon which may contribute to the pathological effects produced by elevated levels of certain endogenous steroids.