title: Comparative study on transcriptional activity of 17 parabens mediated by estrogen receptor α and β and androgen receptor.
abstract: The structure-activity relationships of parabens which are widely used as preservatives for transcriptional activities mediated by human estrogen receptor α (hERα), hERβ and androgen receptor (hAR) were investigated. Fourteen of 17 parabens exhibited hERα and/or hERβ agonistic activity at concentrations of ≤ 1 × 10(-5)M, whereas none of the 17 parabens showed AR agonistic or antagonistic activity. Among 12 parabens with linear alkyl chains ranging in length from C₁ to C₁₂, heptylparaben (C₇) and pentylparaben (C₅) showed the most potent ERα and ERβ agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C₁ or lengthened to C₁₂. Most parabens showing estrogenic activity exhibited ERβ-agonistic activity at lower concentrations than those inducing ERα-agonistic activity. The estrogenic activity of butylparaben was markedly decreased by incubation with rat liver microsomes, and the decrease of activity was blocked by a carboxylesterase inhibitor. These results indicate that parabens are selective agonists for ERβ over ERα; their interactions with ERα/β are dependent on the size and bulkiness of the alkyl groups; and they are metabolized by carboxylesterases, leading to attenuation of their estrogenic activity.
authors.affiliation: Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kojima
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Naoto
authors.initials: N
authors.lastname: Uramaru
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kitamura
mesh_terms: D059002:Androgen Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007536:Isomerism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010226:Parabens / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: C410798:AR protein, human; D059002:Androgen Receptor Antagonists; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010226:Parabens; D011944:Receptors, Androgen; C038091:butylparaben