Changes in thyroid peroxidase activity in response to various chemicals.
Thyroperoxidase (TPO) is a large heme-containing glycoprotein that catalyzes the transfer of iodine to thyroglobulin during thyroid hormone (TH) synthesis. Previously, we established an in vitro assay for TPO activity based on human recombinant TPO (hrTPO) stably transfected into human follicular thyroid carcinoma (FTC-238) cells. It is important to determine whether environmental chemicals can disrupt TPO activity because it is an important factor in the TH axis. In this study, we used our assay to examine the changes in TPO activity in response to various chemicals, including benzophenones (BPs), polycyclic aromatic hydrocarbons (PAHs), and persistent organic pollutants (POPs). Overall, BPs, PAHs, and POPs slightly altered TPO activity at low doses, as compared with the positive controls methimazole (MMI), genistein, and 2,2',4,4'-tetrahydroxy BP. Benzophenone, benzhydrol, 3-methylchloranthracene, pyrene, benzo(k)fluoranthene, benzo(e)pyrene, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and heptachlor decreased TPO activity, while 2,4-dihydroxy BP, 2,2'-dihydroxy-4-methoxy BP, and dibenzo(a,h)anthracene increased TPO activity. From these data, we can predict the disruption of TPO activity by various chemicals as a sensitive TH end point. TPO activity should be considered when enacting measures to regulate environmental exposure to thyroid-disrupting chemicals.
Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology (KIST), P.O. Box 131, Cheongryang, Seoul, Korea.
Mee
M
Song
Youn-Jung
YJ
Kim
Yong-Keun
YK
Park
Jae-Chun
JC
Ryu
D002460:Cell Line; D052244:Endocrine Disruptors / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity; D006801:Humans; D008713:Methimazole / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D018570:Risk Assessment; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism
D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D005466:Fluorocarbons; D011084:Polycyclic Aromatic Hydrocarbons; D013963:Thyroid Hormones; D008713:Methimazole; D013954:Thyroglobulin; D009195:Peroxidase