Thyroid-stimulating hormone-thyroid hormone signaling contributes to circadian regulation through repressing clock2/npas2 in zebrafish  

作　　者：Cheng Ji Yue Ou Wangjianfei Yu Jiaxin Lv Fanmiao Zhang Huashan Li Zeyun Gu Jiayuan Li Zhaomin Zhong Han Wang 

机构地区：[1]Center for Circadian Clocks,Soochow University,Suzhou,Jiangsu 215123,China [2]School of Biology and Basic Medical Sciences,Suzhou Medical College,Soochow University,Suzhou,Jiangsu 215123,China

出　　处：《Journal of Genetics and Genomics》2024年第1期61-74,共14页遗传学报（英文版）

基　　金：supported by grants from the National Key Research and Development Program of China(2019YFA0802400);the National Natural Science Foundation of China(NSFC)(#31300969,#31961133026,#31871187);the Natural Science Foundation of Jiangsu Province(BK20130302),a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PARD).

摘　　要：Thyroid-stimulating hormone(TSH)is important for the thyroid gland,development,growth,and metabolism.Defects in TSH production or the thyrotrope cells within the pituitary gland cause congenital hypothyroidism(CH),resulting in growth retardation and neurocognitive impairment.While human TSH is known to display rhythmicity,the molecular mechanisms underlying the circadian regulation of TSH and the effects of TSH-thyroid hormone(TH)signaling on the circadian clock remain elusive.Here we show that TSH,thyroxine(T4),triiodothyronine(T3),and tshba display rhythmicity in both larval and adult zebrafish and tshba is regulated directly by the circadian clock via both E′-box and D-box.Zebrafish tshba^(−/−)mutants manifest congenital hypothyroidism,with the characteristics of low levels of T_(4)and T_(3)and growth retardation.Loss or overexpression of tshba alters the rhythmicity of locomotor activities and expression of core circadian clock genes and hypothalamic-pituitary-thyroid(HPT)axis-related genes.Furthermore,TSH-TH signaling regulates clock2/npas2 via the thyroid response element(TRE)in its promoter,and transcriptome analysis reveals extensive functions of Tshba in zebrafish.Together,our results demonstrate that zebrafish tshba is a direct target of the circadian clock and in turn plays critical roles in circadian regulation along with other functions.

关 键 词：Thyroid-stimulating hormone subunitβa (tshba) Thyroid hormone Circadian rhythm TALEN ZEBRAFISH 

分 类 号：Q954.4[生物学—动物学]