PUBLICATION
Thyroid-stimulating hormone (TSH)-thyroid hormone (TH) signaling contributes to circadian regulation through repressing clock2/npas2 in zebrafish
- Authors
- Ji, C., Ou, Y., Yu, W., Lv, J., Zhang, F., Li, H., Gu, Z., Li, J., Zhong, Z., Wang, H.
- ID
- ZDB-PUB-230617-39
- Date
- 2023
- Source
- Journal of genetics and genomics = Yi chuan xue bao 51(1): 61-74 (Journal)
- Registered Authors
- Ji, Cheng, Wang, Han, Zhang, Fanmiao, Zhong, Zhaomin
- Keywords
- TALEN, circadian rhythm, thyroid hormone, thyroid-stimulating hormone subunit β a (tshba), zebrafish
- MeSH Terms
-
- Adult
- Animals
- Congenital Hypothyroidism*
- Growth Disorders
- Humans
- Thyrotropin*
- Triiodothyronine/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 37328030 Full text @ J. Genet. Genomics
Citation
Ji, C., Ou, Y., Yu, W., Lv, J., Zhang, F., Li, H., Gu, Z., Li, J., Zhong, Z., Wang, H. (2023) Thyroid-stimulating hormone (TSH)-thyroid hormone (TH) signaling contributes to circadian regulation through repressing clock2/npas2 in zebrafish. Journal of genetics and genomics = Yi chuan xue bao. 51(1):61-74.
Abstract
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, T4, 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 retardation. Loss of tshba 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 TRE in its promoter, and transcriptome analysis revealed 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping