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. 1982 May;79(10):3320–3324. doi: 10.1073/pnas.79.10.3320

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

R Bucala, J Fishman, A Cerami
PMCID: PMC346407  PMID: 6808508

Abstract

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.

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Selected References

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