{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:49:21Z","timestamp":1790700561964,"version":"4.1.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10]]},"abstract":"\n The intra-tissue levels of thyroid hormones (THs) regulate organ functions. Environmental factors can impair these levels by damaging the thyroid gland and\/or peripheral TH metabolism. We investigated the effects of embryonic and\/or long-life exposure to low-dose pesticides, ethylene thiourea (ETU), chlorpyrifos (CPF) and both combined on intra-tissue T\n 4<\/jats:sub>\n \/T\n 3<\/jats:sub>\n metabolism\/signaling in zebrafish at different life stages. Hypothyroidism was evident in exposed larvae that showed reduced number of follicles and induced\n tshb<\/jats:italic>\n mRNAs. Despite that, we found an increase in free T\n 4<\/jats:sub>\n (fT4) and free T\n 3<\/jats:sub>\n (fT3) levels\/signaling that was confirmed by transcriptional regulation of TH metabolic enzymes (deiodinases) and T3-regulated mRNAs (\n cpt1<\/jats:italic>\n ,\n igfbp1a<\/jats:italic>\n ). Second-generation larvae showed that thyroid and TH signaling was affected even when not directly exposed, suggesting the role of parental exposure. In adult zebrafish, we found that sex-dependent damage of hepatic T\n 3<\/jats:sub>\n level\/signaling was associated with liver steatosis, which was more pronounced in females, with sex-dependent alteration of transcripts codifying the key enzymes involved in \u2018\n de novo<\/jats:italic>\n lipogenesis\u2019 and \u03b2-oxidation. We found impaired activation of liver T\n 3<\/jats:sub>\n and PPAR\u03b1\/Foxo3a pathways whose deregulation was already involved in mammalian liver steatosis. The data emphasizes that the intra-tissue imbalance of the T\n 3<\/jats:sub>\n level is due to thyroid endocrine disruptors (THDC) and suggests that the effect of a slight modification in T\n 3<\/jats:sub>\n signaling might be amplified by its direct regulation or crosstalk with PPAR\u03b1\/Foxo3a pathways. Because T\n 3<\/jats:sub>\n levels define the hypothyroid\/hyperthyroid status of each organ, our findings might explain the pleiotropic and site-dependent effects of pesticides.\n <\/jats:p>","DOI":"10.1530\/joe-20-0134","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T10:07:51Z","timestamp":1595498871000},"page":"53-68","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":11,"title":["Peripheral T3 signaling is the target of pesticides in zebrafish larvae and adult liver"],"prefix":"10.1530","volume":"247","author":[{"given":"Marco","family":"Colella","sequence":"first","affiliation":[{"name":"1Department of Science and Technology, University of Sannio, Benevento, Italy"},{"name":"2IRGS, Biogem, Ariano Irpino, Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Nittoli","sequence":"additional","affiliation":[{"name":"2IRGS, Biogem, Ariano Irpino, Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonsina","family":"Porciello","sequence":"additional","affiliation":[{"name":"2IRGS, Biogem, Ariano Irpino, Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immacolata","family":"Porreca","sequence":"additional","affiliation":[{"name":"3Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Reale","sequence":"additional","affiliation":[{"name":"2IRGS, Biogem, Ariano Irpino, Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Russo","sequence":"additional","affiliation":[{"name":"2IRGS, Biogem, Ariano Irpino, Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Antonino","family":"Russo","sequence":"additional","affiliation":[{"name":"2IRGS, Biogem, Ariano Irpino, Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Roberto","sequence":"additional","affiliation":[{"name":"2IRGS, Biogem, Ariano Irpino, Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Albano","sequence":"additional","affiliation":[{"name":"2IRGS, Biogem, Ariano Irpino, Avellino, Italy"},{"name":"4IEOS-CNR, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"De Felice","sequence":"additional","affiliation":[{"name":"4IEOS-CNR, Naples, Italy"},{"name":"5Molecular Medicine and Medical Biotechnologies, University of Naples \u2018Federico II\u2019, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mallardo","sequence":"additional","affiliation":[{"name":"5Molecular Medicine and Medical Biotechnologies, University of Naples \u2018Federico II\u2019, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Ambrosino","sequence":"additional","affiliation":[{"name":"1Department of Science and Technology, University of Sannio, Benevento, Italy"},{"name":"2IRGS, Biogem, Ariano Irpino, Avellino, Italy"},{"name":"4IEOS-CNR, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/247\/1\/JOE-20-0134.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/247\/1\/JOE-20-0134.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:57:12Z","timestamp":1784555832000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/247\/1\/53-68\/5378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/joe-20-0134","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10]]}}}