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

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

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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.

Thyroid-stimulating hormone subunit β a(tshba)Thyroid hormoneCircadian rhythmTALENZebrafish

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

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Center for Circadian Clocks,Soochow University,Suzhou,Jiangsu 215123,China

School of Biology and Basic Medical Sciences,Suzhou Medical College,Soochow University,Suzhou,Jiangsu 215123,China

National Key Research and Development Program of ChinaNational Natural Science Foundation of China(NSFC)National Natural Science Foundation of China(NSFC)National Natural Science Foundation of China(NSFC)Natural Science Foundation of Jiangsu ProvincePriority Academic Program Development of Jiangsu Higher Education Institutions(PARD)

2019YFA0802400313009693196113302631871187BK20130302

2024

10.1016/j.jgg.2023.05.015

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(1)
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