The ultraviolet filter benzophenone 2 interferes with the thyroid hormone axis in rats and is a potent in vitro inhibitor of human recombinant thyroid peroxidase.
Endocrine disrupting chemicals (EDCs), either plant constituents or contaminants deriving from industrial products, may interfere with the thyroid hormone (TH) axis. Here, we examined whether selected EDCs inhibit the key reactions of TH biosynthesis catalyzed by thyroid peroxidase (TPO). We used a novel in vitro assay based on human recombinant TPO (hrTPO) stably transfected into the human follicular thyroid carcinoma cell line FTC-238. F21388 (synthetic flavonoid), bisphenol A (building block for polycarbonates), and the UV filter benzophenone 2 (BP2) inhibited hrTPO. BP2 is contained in numerous cosmetics of daily use and may be in regular contact with human skin. Half-maximal inhibition in the guaiacol assay occurred at 450 nmol/liter BP2, a concentration 20- and 200-fold lower than those required in case of the TPO-inhibiting antithyroid drugs methimazole and propylthiouracil, respectively. BP2 at 300 nmol/liter combined with the TPO substrate H(2)O(2) (10 mumol/liter) inactivated hrTPO; this was, however, prevented by micromolar amounts of iodide. BP2 did not inhibit iodide uptake into FRTL-5 cells. In BP2-treated rats (333 and 1000 mg/kg body weight), serum total T(4) was significantly decreased and serum thyrotropin was significantly increased. TPO activities in the thyroids of treated animals were unchanged, a finding also described for methimazole and propylthiouracil. Thus, EDCs, most potently BP2, may disturb TH homeostasis by inhibiting or inactivating TPO, effects that are even more pronounced in the absence of iodide. This new challenge for endocrine regulation must be considered in the context of a still prevailing iodide deficiency in many parts of the world.
Schmutzler
Cornelia
C
Institut für Experimentelle Endokrinologie, Charité Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany. cornelia.schmutzler@charite.de
Bacinski
Anja
A
Gotthardt
Inka
I
Huhne
Katrin
K
Ambrugger
Petra
P
Klammer
Holger
H
Schlecht
Christiane
C
Hoang-Vu
Cuong
C
Grüters
Annette
A
Wuttke
Wolfgang
W
Jarry
Hubertus
H
Köhrle
Josef
J
D000818:Animals; D001324:Autoantigens; D001577:Benzophenones / Q000633:toxicity*; D002457:Cell Extracts / Q000032:analysis; D002478:Cells, Cultured; D052244:Endocrine Disruptors / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005374:Filtration; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors*; D007455:Iodine / Q000378:metabolism / Q000494:pharmacology; D033862:Iron-Binding Proteins / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013963:Thyroid Hormones / Q000378:metabolism*; D014466:Ultraviolet Rays
D001324:Autoantigens; D001577:Benzophenones; D002457:Cell Extracts; D052244:Endocrine Disruptors; D033862:Iron-Binding Proteins; D011994:Recombinant Proteins; D013963:Thyroid Hormones; D007455:Iodine; D006861:Hydrogen Peroxide; C056658:TPO protein, human; D007453:Iodide Peroxidase; C035476:2,2',4,4'-tetrahydroxybenzophenone