CoChat
Sign Up
Cited by 21Estrogen and related hormone effectsHypothalamic control of reproductive hormonesRegulation of Appetite and Obesity

Regulation of gene expression by 17β-estradiol in the arcuate nucleus of the mouse through ERE-dependent and ERE-independent mechanisms

Open access
Yang, Jennifer A., Mamounis, Kyle J., Yasrebi, Ali, Roepke, Troy A.·2016·Steroids
DOI 10.1016/j.steroids.2016.01.003PMC PMC4775315
Open this paper in CoChat — free account

Abstract

17β-Estradiol (E2) modulates gene expression in the hypothalamic arcuate nucleus (ARC) to control homeostatic functions. In the ARC, estrogen receptor (ER) α is highly expressed and is an important contributor to E2's actions, controlling gene expression through estrogen response element (ERE)-dependent and -independent mechanisms. The objective of this study was to determine if known E2-regulated genes are regulated through these mechanisms. The selected genes have been shown to regulate homeostasis and have been separated into three subsections: channels, receptors, and neuropeptides. To determine if ERE-dependent or ERE-independent mechanisms regulate gene expression, two transgenic mouse models, an ERα knock-out (ERKO) and an ERα knock-in/knock-out (KIKO), which lacks a functional ERE binding domain, were used in addition to their wild-type littermates. Females of all genotypes were ovariectomized and injected with oil or estradiol benzoate (E2B). Our results suggest that E2B regulates multiple genes through these mechanisms. Of note, Cacna1g and Kcnmb1 channel expression was increased by E2B in WT females only, suggesting an ERE-dependent regulation. Furthermore, the NKB receptor, Tac3r, was suppressed by E2B in WT and KIKO females but not ERKO females, suggesting that ERα-dependent, ERE-independent signaling is necessary for Tac3r regulation. The adrenergic receptor Adra1b was suppressed by E2B in all genotypes indicating that ERα is not the primary receptor for E2B's actions. The neuropeptide Tac2 was suppressed by E2B through ERE-dependent mechanisms. These results indicate that E2B activates both ERα-dependent and independent signaling in the ARC through ERE-dependent and ERE-independent mechanisms to control gene expression.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.steroids.2016.01.003

Cites

86 of 86 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In females, ARC kisspeptin expression is suppressed by ERα-mediated ERE-independent mechanisms or de-repressed via a hormone response element.

    “In females, ARC kisspeptin expression is suppressed through ERα-mediated, ERE-independent mechanisms or de-repressed through a hormone response element44,46.”

    From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [44]

    The Results and Discussion (page not provided) show that estradiol suppresses ARC Kiss1 expression in female mice through an ERα-mediated, ERE-independent mechanism. The Discussion notes that the mouse model may permit signaling through other hormone response elements, but it does not show that ARC kisspeptin expression is de-repressed through one. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Both kisspeptin populations have ERα and low ERβ but respond differently to E2 via ERE-dependent and ERE-independent mechanisms.

    “Both populations of kisspeptin neurons express ERα (with low ERβ expression) but respond differentially to E2 through ERE-dependent and ERE-independent mechanisms44,45.”

    From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [44]

    The Discussion identifies kisspeptin populations in the AVPV and ARC, and reports E2 regulation of ARC Kiss1 through an ERE-independent mechanism. It also says ERα is more highly expressed than ERβ in the ARC. The paper does not establish ERα and low ERβ expression in both kisspeptin populations or compare their E2 responses through these mechanisms; its study focuses on the ARC. Page numbers are unavailable in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Neurokinin B and dynorphin, co-expressed with kisspeptin in ARC KNDy neurons, are downregulated by E2 via ERα-mediated ERE-dependent mechanisms.

    “Neurokinin B and dynorphin, co-expressed with kisspeptin (KNDy neurons) in the ARC nucleus and vital components of the GnRH pulse generator, are also downregulated by E2 but through ERα-mediated, ERE-dependent mechanisms44,45.”

    From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [44]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Yang, J. A., Mamounis, K. J., Yasrebi, A., & Roepke, T. A.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
Roepke, Troy A.
ORCID
Venue
Steroids
Publisher
Elsevier BV
Published
2016-03
Volume
107
Pages
128-138
ISSN
0039-128X (ISSN-L)
DOI
10.1016/j.steroids.2016.01.003
PMC
PMC4775315
OpenAlex
W2229546028
Cited by
21
References
86
Citations by year
2025: 6 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 2
FWCI
2.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Steroids (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Rutgers University Community Repository (Rutgers University) (acceptedVersion)
  • Rutgers University Community Repository (Rutgers University)
Funders
  • National Institutes of Health (R00DK083457, NJ06107, U54-HD298934)
  • University of Virginia
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
estradiol, arcuate nucleus, estrogen receptor alpha, estrogen response element, gene expression regulation, CACNA1G, KCNMB1, ovariectomy, estradiol benzoate, hypothalamus, homeostasis
MeSH terms
Animals, Arcuate Nucleus of Hypothalamus, Estradiol, Female, Gene Expression Regulation, Nerve Tissue Proteins, Mice, Knockout, Estrogen Receptor alpha, Mice, Gene Knock-In Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review