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Citations to this article

Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling
Mark Harris, … , Jeffrey S. Flier, Anthony N. Hollenberg
Mark Harris, … , Jeffrey S. Flier, Anthony N. Hollenberg
Published January 1, 2001
Citation Information: J Clin Invest. 2001;107(1):111-120. https://doi.org/10.1172/JCI10741.
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Article

Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling

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Abstract

Starvation causes a rapid reduction in thyroid hormone levels in rodents. This adaptive response is caused by a reduction in thyrotropin-releasing hormone (TRH) expression that can be reversed by the administration of leptin. Here we examined hypothalamic signaling pathways engaged by leptin to upregulate TRH gene expression. As assessed by leptin-induced expression of suppressor of cytokine signaling–3 (SOCS-3) in fasted rats, TRH neurons in the paraventricular nucleus are activated directly by leptin. To a greater degree, they also contain melanocortin-4 receptors (MC4Rs), implying that leptin can act directly or indirectly by increasing the production of the MC4R ligand, α-melanocyte stimulating hormone (α-MSH), to regulate TRH expression. We further demonstrate that both pathways converge on the TRH promoter. The melanocortin system activates the TRH promoter through the phosphorylation and DNA binding of the cAMP response element binding protein (CREB), and leptin signaling directly regulates the TRH promoter through the phosphorylation of signal transducer and activator of transcription 3 (Stat3). Indeed, a novel Stat-response element in the TRH promoter is necessary for leptin’s effect. Thus, the TRH promoter is an ideal target for further characterizing the integration of transcriptional pathways through which leptin acts.

Authors

Mark Harris, Carl Aschkenasi, Carol F. Elias, Annie Chandrankunnel, Eduardo A. Nillni, Christian Bjørbæk, Joel K. Elmquist, Jeffrey S. Flier, Anthony N. Hollenberg

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 Total
Citations: 2 4 4 6 6 3 7 4 4 3 7 7 9 10 8 6 6 3 2 3 3 3 2 1 113
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2014 (7)

Title and authors Publication Year
Differential expression of the melanocortin-4 receptor in male and female C57BL/6J mice
HE Qu, JP Li, W Chen, YM Li, Q Jiang, HZ Jiang, JL Huo, ZH Zhao, B Liu, QL Zhang
Molecular Biology Reports 2014
CREB/TRH pathway in the central nervous system regulates energy expenditure in response to deprivation of an essential amino acid
T Xia, Q Zhang, Y Xiao, C Wang, J Yu, H Liu, B Liu, Y Zhang, S Chen, Y Liu, Y Chen, F Guo
International Journal of Obesity 2014
Effect of Sleeve Gastrectomy on Thyroid Hormone Levels
Y Abu-Ghanem, R Inbar, V Tyomkin, I Kent, L Berkovich, R Ghinea, S Avital
Obesity Surgery 2014
Thyroid Hormone and Leptin in the Testis
CF Ramos, A Zamoner
Frontiers in Endocrinology 2014
Leptin Induces Hippocampal Synaptogenesis via CREB-Regulated MicroRNA-132 Suppression of p250GAP
M Dhar, M Zhu, S Impey, TJ Lambert, T Bland, IN Karatsoreos, T Nakazawa, SM Appleyard, GA Wayman
Molecular Endocrinology 2014
Central Regulation of Hypothalamic-Pituitary-Thyroid Axis Under Physiological and Pathophysiological Conditions
C Fekete, RM Lechan
Endocrine reviews 2014
A novel form of ciliopathy underlies hyperphagia and obesity in Ankrd26 knockout mice
P Acs, PO Bauer, B Mayer, T Bera, R Macallister, E Mezey, I Pastan
Brain structure & function 2014

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