title: Waterborne exposure to microcystin-LR alters thyroid hormone levels and gene transcription in the hypothalamic-pituitary-thyroid axis in zebrafish larvae.
abstract: Microcystin-leucine-arginine (MCLR) is the most toxic and the most commonly encountered variant of microcystins (MCs) in aquatic environment, and it has the potential for disrupting thyroid hormone homeostasis, but the molecular mechanisms underlying this process have not yet been clarified. In the present study, we observed body growth retardation associated with decreased levels of thyroid hormones (THs) in zebrafish larvae, highlighting the interferences of MCLR with the growth of fish larvae. To further our understanding of mechanisms of MCLR-induced endocrine toxicity, quantitative real-time PCR analysis was performed on hypothalamic-pituitary-thyroid (HPT) axis related genes of developing zebrafish embryos exposed to 100, 300 and 500 μg L(-1) MCLR until 96 h post-fertilization. The expression of several genes in the HPT system, i.e., corticotropin-releasing factor (CRF), thyroid-stimulating hormone (TSH), sodium/iodide symporter (NIS), thyroglobulin (TG), thyroid receptors (TRα and TRβ) and iodothyronine deiodinases (Dio1 and Dio2) was examined using quantitatively real-time PCR. The gene expression levels of CRF, TSH, NIS and TG were significantly induced after exposure to 500 μg L(-1) MCLR. The transcription of TRs gene was down-regulated in a concentration-dependent manner. Up-regulation and down-regulation of Deio1 and Deio2 gene expression, respectively, were observed upon exposure to MCLR. The above results indicated that MCLR could alter gene expression in the HPT axis which might subsequently contribute to MCLR-induced thyroid disruption.
authors.affiliation: Institute of Agricultural Quality Standards & Testing Technology, Hubei Academy of Agricultural Sciences, Wuhan 430064, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Shuqian
authors.initials: S
authors.lastname: Li
authors.forename: Dingjin
authors.initials: D
authors.lastname: Hu
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D015536:Down-Regulation; D004781:Environmental Exposure; D015870:Gene Expression / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D013963:Thyroid Hormones; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; C057862:cyanoginosin LR