标题：Formation of covalent adducts between cortisol and 16 alpha-hydroxyestrone and protein: possible role in the pathogenesis of cortisol toxicity and systemic lupus erythematosus.
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1982
卷号：79
期号：10
页码：3320-3324
DOI：10.1073/pnas.79.10.3320
出版社：The National Academy of Sciences of the United States of America
摘要：The incubation of 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. It is hypothesized that a Heyns rearrangement involving the adjacent hydroxyl group traps the Schiff base and produces a stable ketoamine adduct. The binding of 16 alpha-hydroxyestrone and cortisol to albumin is significantly inhibited by acetylsalicylic acid, which has been shown to acetylate 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. We propose that 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.
