{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T15:13:43Z","timestamp":1771168423868,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"name":"Neurological and Endocrine Toxicology Branch of the Center for Public Health and Environmental Assessment in the Office of Research and Development in Research Triangle Park"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We recently identified the herbicide oxyfluorfen as an inhibitor of iodide uptake by the sodium iodide symporter, a key step in thyroid hormone synthesis, using in vitro assays. We also observed a suppression of serum T4 and T3 in juvenile rats exposed orally to oxyfluorfen for 4 to 8-d. The purpose of the present study was to further evaluate the effects of an extended 31-d oral exposure using a male pubertal rat study (15 to 500\u2009mg\/kg). Oxyfluorfen delayed puberty at all doses (1.3 to 3.5-d) suppressing ventral prostate at 62.5\u2009mg\/kg and above and seminal vesicle weights at 31.25\u2009mg\/kg and above with no effect on testosterone or luteinizing hormone. Serum T4 and T3 were suppressed by all doses up to 80%, with a linear increase in serum TSH. Based on delayed puberty without changes in testosterone, we hypothesized that oxyfluorfen interferes with androgen receptor (AR) function. Results from our Hershberger study, with oxyfluorfen (62.5 and 125\u2009mg\/kg) co-treated with testosterone propionate (TP, 1\u2009mg\/kg) for 10-d showed 3 of 5 of the androgenic tissue weights were suppressed compared with TP alone indicating AR antagonism. We next confirmed this effect in an in vitro AR transcriptional activation reporter assay (0 to 20\u2009\u03bcM) with 125\u2009pM 5\u03b1DH-11-ketotestosterone and found concentration-dependent inhibition of AR luminescence activity (EC50 1.75\u2009\u00b5M) without cytotoxicity. Thus, this study confirms the endocrine-disrupting mechanism of oxyfluorfen using in vitro and in vivo evaluations of the thyroid hormone and AR pathways. This abstract does not necessarily reflect U.S. EPA policy.<\/jats:p>","DOI":"10.1093\/toxsci\/kfae144","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T15:07:11Z","timestamp":1730732831000},"page":"206-215","source":"Crossref","is-referenced-by-count":4,"title":["Peripubertal exposure to oxyfluorfen, a diphenyl herbicide, delays pubertal development in the male rat by antagonizing androgen receptor activity"],"prefix":"10.1093","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0179-8689","authenticated-orcid":false,"given":"Ashley S","family":"Murr","sequence":"first","affiliation":[{"name":"Neurological and Endocrine Toxicology Branch, Public Health and Integrated Toxicology Division, CPHEA, ORD, U.S. EPA , Research Triangle Park, NC 27711,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela R","family":"Buckalew","sequence":"additional","affiliation":[{"name":"Neurological and 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