Subglutinol A is an immunosuppressive alpha-pyrone diterpenoid isolated from Fusarium subglutinans that exhibits osteogenic activity. Several non-steroid mycotoxins isolated from various strains of Fusarium fungi exhibit female steroid hormone activities. In this study, we characterized the estrogenic activity of subglutinol A (1). Subglutinol A blocked the 17 beta-estradiol-induced activation of reporter plasmids and endogenous estrogen-responsive target genes in a dose-dependent manner and efficiently destabilized ER proteins as shown using the estrogen receptor antagonist ICI 182,780. Subglutinol A also displaced the specific binding of [H-3]17 beta-estradiol from ER in MCF-7 whole-cell ligand binding assays. These data demonstrate the potential of subglutinol A as an ER antagonist though its competition with 17 beta-estradiol for direct ER association. (C) 2015 Elsevier Inc. All rights reserved.