title: Anti-androgenic properties of Compound A, an analog of a non-steroidal plant compound.
abstract: We investigated the interactions between Compound A (CpdA), an analog of a hydroxyphenyl aziridine precursor found in an African shrub, and the androgen receptor (AR). CpdA represses androgen-induced activation of both specific and non-specific androgen DNA response elements. While a similar effect was obtained for the progesterone receptor (PR) via a non-specific hormone response element, CpdA had no effect on the actions of the glucocorticoid and mineralocorticoid receptors. CpdA represses the ligand-dependent interaction between the NH(2)- and COOH-terminal domains of the AR, similar to well-characterised anti-androgens. CpdA also interferes with the interaction of steroid receptor co-activator 1 (SRC1) with the activation domain AF2 but not with AF1. However, CpdA does not compete with androgen for binding to the AR. These results demonstrate that CpdA elicits anti-androgenic actions by a mechanism other than competitive binding for the AR.
authors.affiliation: Department of Biochemistry, University of Stellenbosch, South Africa.
authors.forename: T M
authors.initials: TM
authors.lastname: Tanner
authors.forename: G
authors.initials: G
authors.lastname: Verrijdt
authors.forename: W
authors.initials: W
authors.lastname: Rombauts
authors.forename: A
authors.initials: A
authors.lastname: Louw
authors.forename: J P
authors.initials: JP
authors.lastname: Hapgood
authors.forename: F
authors.initials: F
authors.lastname: Claessens
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005021:Ethylamines / Q000494:pharmacology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D000882:Haplorhini; D051548:Histone Acetyltransferases; D006801:Humans; D008024:Ligands; D008297:Male; D056920:Nuclear Receptor Coactivator 1; D010944:Plants / Q000737:chemistry; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014439:Tyramine / Q000031:analogs & derivatives
chemical_list: C104564:2-(4-acetoxyphenyl)-2-chloro-N-methylethylamine; D000085:Acetates; D000726:Androgen Antagonists; D000728:Androgens; D005021:Ethylamines; D008024:Ligands; D011944:Receptors, Androgen; D014157:Transcription Factors; D004247:DNA; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D017430:Prostate-Specific Antigen; D014439:Tyramine