Phenylphenols, biphenols, bisphenol-A and 4- tert-octylphenol exhibit α and β estrogen activities and antiandrogen activity in reporter cell lines

• Published in: Molecular and cellular endocrinology 2002-07, Vol.193 (1), p.43-49
• Main Authors: Paris, Françoise, Balaguer, Patrick, Térouanne, Béatrice, Servant, Nadège, Lacoste, Caroline, Cravedi, Jean-Pierre, Nicolas, Jean-Claude, Sultan, Charles
• Format: Article
• Language: English
• Subjects: 4,4′ Biphenol; 4- tert-Octylphenol; Androgen receptor; Androgen Receptor Antagonists; Benzhydryl Compounds; Biphenyl Compounds - pharmacology; Bisphenol-A; Cell Line; Dose-Response Relationship, Drug; Endocrine disruptors; Environmental Pollutants - pharmacology; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen receptors; Estrogens, Non-Steroidal - pharmacology; Genes, Reporter; Humans; Phenols - chemistry; Phenols - pharmacology; Radioligand Assay; Receptors, Androgen - genetics; Receptors, Estrogen - agonists; Receptors, Estrogen - genetics; Transfection
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(02)00094-1

We previously demonstrated the interactions of different chemical compounds with estrogen receptors ERα and ERβ and the androgen receptor (AR) using different reporter cell lines. In this study, we characterize the ERα, ERβ and AR activity of different biphenyls using the same tools. We provide evidence that several phenyl derivatives present both estrogenic and antiandrogenic activity. The extent of hydroxylation and the position of the hydroxyl function were important in determining their estrogenicity and antiandrogenicity. Of the tested compounds, bisphenol-A and 4,4′ biphenol had very high estrogenic activity, although it was lower than that of the strong estrogenic alkylphenol, 4- tert-octylphenol. Bisphenol-A and 4,4′ biphenol were able to activate ERs at concentrations lower than 1 μM, whereas the other compounds only activated at concentrations above 1 μM. Interestingly, 4,4′ biphenol was a better agonist for ERβ than for ERα. No androgenic activity was detected for any of these compounds. Bisphenol-A, 3-OH phenylphenol, 4-OH phenylphenol and 4,4′ biphenol exhibited antiandrogenic activity close to that of 4- tert-octylphenol (IC 50≈5 μM). In whole cell binding assays, these compounds displaced [ 3H] R1881 with Ki=10 μM. Although these Ki values seem high in comparison with that of hydroxyflutamide (0.4 μM), one must keep in mind that environmental chemicals can accumulate in adipose tissues for several years. In conclusion, these environmental chemicals may have a negative impact on androgen action during fetal and post-natal life.