Cited by 75Estrogen and related hormone effectsRegulation of Appetite and ObesityHypothalamic control of reproductive hormones

The estrogen receptor α colocalizes with proopiomelanocortin in hypothalamic neurons and binds to a conserved motif present in the neuron-specific enhancer nPE2

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de Souza, Flávio S.J., Nasif, Sofia, López-Leal, Rodrigo, Levi, Diego H., Low, Malcolm J., Rubinsten, Marcelo·2011·European Journal of Pharmacology

Abstract

The gene encoding the prohormone proopiomelanocortin (POMC) is mainly expressed in two regions in vertebrates, namely corticotrophs and melanotrophs in the pituitary and a small population of neurons in the arcuate nucleus of the hypothalamus. In this latter region, POMC-derived peptides participate in the control of energy balance and sensitivity to pain. Neuronal expression of POMC is conferred by two enhancers, nPE1 and nPE2, which are conserved in most mammals, but no transcription factors are yet known to bind to these enhancers. In this work, by means of a one-hybrid screening, we identify that nPE2 possesses an element recognized by transcription factors of the nuclear receptor superfamily. This element, named NRBE, is conserved in all known nPE2 enhancers and is necessary to confer full enhancer strength to nPE2-driven reporter gene expression in transgenic mice assays, indicating that the phylogenetic conservation of the element is indicative of its functional importance. In a search for candidate nuclear receptors that might control POMC we observed that estrogen receptor alpha (ESR1) - a known regulator of energy balance at the hypothalamic level - can bind to the NRBE element in vitro. In addition we observed by immunofluorescence that ESR1 is coexpressed with POMC in around 25-30% of hypothalamic neurons of males and females during late embryonic stages and adulthood. Thus, our results indicate that hypothalamic expression of POMC is controlled by nuclear receptors and establish ESR1 as a candidate regulator of POMC.

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  • NPY exhibits decreased orexigenic activity after exposure to estrogens, due to estrogen modulation of NPY mRNA expression and receptor activity.

    “NPY exhibits decrease orexigenic activity after exposure to estrogens. This inhibitory action is due to the estrogen modulation of NPY mRNA expression and receptor activity [93, 94].”

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Authors
de Souza, F. S. J., Nasif, S., López-Leal, R., Levi, D. H., Low, M. J., & Rubinsten, M.
Affiliations
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
  • University of Michigan (US)
Corresponding author
Rubinsten, Marcelo
Venue
European Journal of Pharmacology
Publisher
Elsevier BV
Published
2011-06
Volume
660
Issue
1
Pages
181-187
ISSN
0014-2999 (ISSN-L)
OpenAlex
W2089174173
Cited by
75
References
39
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 3 · 2019: 10 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 8 · 2012: 4
FWCI
3.99
Type
journal article
Language
en
Open access
Locations
  • European Journal of Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068400, DK068400)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
estrogen receptor alpha, proopiomelanocortin, hypothalamic neurons, arcuate nucleus, transcriptional regulation, energy balance, melanotrophs, corticotrophs, colocalization, enhancer conservation
MeSH terms
Animals, Base Sequence, Enhancer Elements, Genetic, Female, Humans, Hypothalamus, Male, Molecular Sequence Data, Neurons, Pro-Opiomelanocortin, Protein Binding, Conserved Sequence, Gene Expression Regulation, Developmental, Protein Transport, Estrogen Receptor alpha, Mice

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