Phthalic acid mimics 17 beta-estradiol actions in WISH cells

The object of this study was to evaluate whether phthalic acid, which is on e of the metabolites of phthalic acid esters, exerts estrogenic actions in WISH cells, an immortalized cell line derived from human amniotic tissue. O ur data demonstrate that phthalic acid (i) displaces [H-3]estradiol from it s binding sites, (ii) enhances the intracellular cyclic AMP concentration, without influencing adenylyl cyclase activity, (iii) stimulates or inhibits prostaglandin output, probably depending on the intracellular nucleotide l evel. The effects on prostanoid release are counteracted by addition of the protein-synthesis inhibitor cycloheximide, or when the diffusion of phthal ic acid through the cell membrane is prevented. On the basis of our previou s demonstration, that 17 beta -estradiol exerts similar effects in WISH cel ls, we suggest that the molecular mechanisms underlying phthalic acid and s teroid-hormone responses in this cell line are the same. This is the first demonstration that phthalic acid binds to the estrogen receptor with high a ffinity and mimics the hormone physiological actions. (C) 2001 Elsevier Sci ence Ireland Ltd. All rights reserved.