ArticleProceedings of the National Academy of Sciences of the United States of America2010
Thyroid hormone exerts negative feedback on hypothalamic type 4 melanocortin receptor expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 77 citations in OpenAlex.
- Roles of thyroid and leptin hormones and their crosstalk in male reproductive functions: an updated review.Endocrine · 2025Review
- Phylogenomic analysis of the Lake Kronotskoe species flock of Dolly Varden charr reveals genetic and developmental signatures of sympatric radiation.Development (Cambridge, England) · 2024Article
- The Downregulation of the Liver Lipid Metabolism Induced by Hypothyroidism in Male Mice: Metabolic Flexibility Favors Compensatory Mechanisms in White Adipose Tissue.International journal of molecular sciences · 2024Article
- Phylogenomic analysis of the Lake Kronotskoe species flock of Dolly Varden charr reveals genetic and developmental signatures of sympatric radiation.bioRxiv : the preprint server for biology · 2024Article
- Thyroid Hormone Clearance in the Paraventricular Nucleus of Male Mice Regulates Lean Mass and Physical Activity.Neuroendocrinology · 2024Article
- Sex Dimorphic Responses of the Hypothalamus-Pituitary-Thyroid Axis to Energy Demands and Stress.Frontiers in endocrinology · 2021Review
- The Role of the Thyroid Axis in Fish.Frontiers in endocrinology · 2020Review
- Evidence for Prenatal Exposure to Thyroid Disruptors and Adverse Effects on Brain Development.European thyroid journal · 2019Review
- Tanycytes and the Control of Thyrotropin-Releasing Hormone Flux Into Portal Capillaries.Frontiers in endocrinology · 2019Review
- Article
- miRNA-125b-5p Suppresses Hypothyroidism Development by Targeting Signal Transducer and Activator of Transcription 3.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Integrating Thyroid Hormone Signaling in Hypothalamic Control of Metabolism: Crosstalk Between Nuclear Receptors.International journal of molecular sciences · 2018Review
- Metabolism Disrupting Chemicals and Alteration of Neuroendocrine Circuits Controlling Food Intake and Energy Metabolism.Frontiers in endocrinology · 2018Review
- Article
- Thyroid hormone and vitamin D regulate VGF expression and promoter activity.Journal of molecular endocrinology · 2016Article
- Deciphering the regulatory logic of an ancient, ultraconserved nuclear receptor enhancer module.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Differential expression of the melanocortin-4 receptor in male and female C57BL/6J mice.Molecular biology reports · 2014Article
- Deciphering direct and indirect influence of thyroid hormone with mouse genetics.Molecular endocrinology (Baltimore, Md.) · 2014Review
- Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions.Endocrine reviews · 2014Review
- Liver X receptor regulation of thyrotropin-releasing hormone transcription in mouse hypothalamus is dependent on thyroid status.PloS one · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The type 4 melanocortin receptor MC4R, a key relay in leptin signaling, links central energy control to peripheral reserve status. MC4R activation in different brain areas reduces food intake and increases energy expenditure. Mice lacking Mc4r are obese. Mc4r is expressed by hypothalamic paraventricular Thyrotropin-releasing hormone (TRH) neurons and increases energy usage through activation of Trh and production of the thyroid hormone tri-iodothyronine (T(3)). These facts led us to test the hypothesis that energy homeostasis should require negative feedback by T(3) on Mc4r expression. Quantitative PCR and in situ hybridization showed hyperthyroidism reduces Mc4r mRNA levels in the paraventricular nucleus. Comparative in silico analysis of Mc4r regulatory regions revealed two evolutionarily conserved potential negative thyroid hormone-response elements (nTREs). In vivo ChIP assays on mouse hypothalamus demonstrated association of thyroid hormone receptors (TRs) with a region spanning one nTRE. Further, in vivo gene reporter assays revealed dose-dependent T(3) repression of transcription from the Mc4r promoter in mouse hypothalamus, in parallel with T(3)-dependent Trh repression. Mutagenesis of the nTREs in the Mc4r promoter demonstrated direct regulation by T(3), consolidating the ChIP results. In vivo shRNA knockdown, TR over-expression approaches and use of mutant mice lacking specific TRs showed that both TRalpha and TRbeta contribute to Mc4r regulation. T(3) repression of Mc4r transcription ensures that the energy-saving effects of T(3) feedback on Trh are not overridden by MC4R activation of Trh. Thus parallel repression by T(3) on hypothalamic Mc4r and Trh contributes to energy homeostasis.
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