Abstract
Thyroid-stimulating hormone(TSH)is important for the thyroid gland,development,growth,and meta-bolism.Defects in TSH production or the thyrotrope cells within the pituitary gland cause congenital hy-pothyroidism(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 T4 and T3 and growth retar-dation.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 tran-scriptome 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 tum plays critical roles in circadian regulation along with other functions.
基金项目
National Key Research and Development Program of China(2019YFA0802400)
National Natural Science Foundation of China(NSFC)(31300969)
National Natural Science Foundation of China(NSFC)(31961133026)
National Natural Science Foundation of China(NSFC)(31871187)
Natural Science Foundation of Jiangsu Province(BK20130302)
Priority Academic Program Development of Jiangsu Higher Education Institutions(PARD)()
NETL
NSTL
维普
万方数据