title: Zebrafish embryos/larvae for rapid determination of effects on hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-interrenal (HPI) axis: mRNA expression.
abstract: To identify and prioritize chemicals that may affect thyroid and adrenal/interregnal endocrine system and to reduce cost and animal use by conventional toxicity assay, an in vivo screening assay was developed using zebrafish embryos/larvae based on measurement of expression of genes that were suggested to play important roles in hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-interrenal (HPI) axis. Model chemicals that could modulate HPT and HPI axis in adult fish were selected in assay validation, including anti-thyroid agent 6-Propyl-2-thiouracil (PTU) and cytochrome P450 11B (Cyp11b) enzyme inhibitor metyrapone (MET). Zebrafish embryos were exposed to different concentrations of model chemical from 4h post-fertilization (hpf) to 5d post-fertilization (dpf). Exposure to PTU increased mRNA expression of sodium iodide symporter (nis) and thyroglobulin (tg) involved in HPT axis, and MET treatment up-regulated all the mRNA expression tested involved in HPI axis by a compensatory mechanism. These results suggested that HPT and HPI axis were active upon chemical exposure at least at 5 dpf zebrafish. Furthermore, we studied the effects of PTU or MET on the cross-talk between HPT and HPI axis. The results demonstrated that PTU and MET could affect cross-talk responses in zebrafish embryos/larvae.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse & School of the Environment, Nanjing University, Nanjing, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Liu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000502:physiology; D004703:Endocrine System / Q000187:drug effects* / Q000502:physiology; D015870:Gene Expression; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000502:physiology; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D014874:Water Pollutants, Chemical
keywords: Chemical screening; Cross-talk; Endocrine disruption; mRNA expression