Cited by 109Hypothalamic control of reproductive hormonesRegulation of Appetite and ObesityReproductive Biology and Fertility

Effects of Leptin and Melanocortin Signaling Interactions on Pubertal Development and Reproduction

Open access
Israel, Davelene D., Sheffer-Babila, Sharone, de Luca, Carl, Jo, Young-Hwan, Liu, Shun Mei, Xia, Qiu, Spergel, Daniel J., Dun, Siok L. +2 more·2012·Endocrinology

Abstract

Leptin and melanocortin signaling control ingestive behavior, energy balance, and substrate utilization, but only leptin signaling defects cause hypothalamic hypogonadism and infertility. Although GnRH neurons do not express leptin receptors, leptin influences GnRH neuron activity via regulation of immediate downstream mediators including the neuropeptides neuropeptide Y and the melanocortin agonist and antagonist, α-MSH, agouti-related peptide, respectively. Here we show that modulation of melanocortin signaling in female db/db mice through ablation of agouti-related peptide, or heterozygosity of melanocortin 4 receptor, restores the timing of pubertal onset, fertility, and lactation. Additionally, melanocortin 4 receptor activation increases action potential firing and induces c-Fos expression in GnRH neurons, providing further evidence that melanocortin signaling influences GnRH neuron activity. These studies thus establish melanocortin signaling as an important component in the leptin-mediated regulation of GnRH neuron activity, initiation of puberty and fertility.

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 · 10.1210/en.2011-1822

Cites

76 of 76 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?

  • α-MSH via MC4 increases GnRH firing, while β-endorphin via μ-opioid receptors inhibits GnRH excitability.

    “α-MSH activation of the melanocortin 4 (MC4) receptor increases GnRH action potential firing while β-endorphin signaling through μ-opioid receptors inhibit GnRH excitability33,59.”

    From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [59]

    In “Activation of melanocortin receptors increases GnRH neuron activity” (page not specified), the paper reports increased GnRH firing after treatment with MTII, an MC3/4 receptor agonist; it also reports MC4R expression in GnRH neurons. It does not establish that α-MSH acting specifically through MC4R caused the firing increase, and the passages found do not address β-endorphin inhibition through μ-opioid receptors (searched: endorphin, opioid). (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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

Authors
Israel, D. D., Sheffer-Babila, S., de Luca, C., Jo, Y.-H., Liu, S. M., Xia, Q., Spergel, D. J., Dun, S. L., Dun, N. J., & Chua, S. C.
Affiliations
  • Departments of Medicine (D.D.I., Y.-H.J., S.M.L., Q.X., S.C.C.), Bronx, New York 10461
  • Albert Einstein College of Medicine (US)
  • Department of Medicine (C.d.L.), Division of Preventive Medicine and Nutrition, Columbia University, New York, New York 10032
  • Yale University (US)
  • Temple University (US)
Corresponding author
Chua, Streamson C.
Venue
Endocrinology
Published
2012-03-09
Volume
153
Issue
5
Pages
2408-2419
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2048438803
Cited by
109
References
76
Citations by year
2026: 4 · 2025: 7 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 8 · 2018: 10 · 2017: 9 · 2016: 3 · 2015: 10 · 2014: 12 · 2013: 14 · 2012: 7
FWCI
16.01
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Diabetes Association
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK057621, P30DK02668, T32DK007513)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD053529, U54HD058155)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords
leptin signaling, melanocortin signaling, melanocortin-4 receptor, agouti-related protein, GnRH neurons, puberty onset, female fertility, hypothalamic hypogonadism, db/db mice, neuropeptide Y, alpha-melanocyte-stimulating hormone, c-fos, lactation, energy balance
MeSH terms
Animals, Blood Glucose, Cell Count, Estradiol, Female, Hypothalamus, Insulin, Neurons, Ovary, Progesterone, Sexual Maturation, Signal Transduction, Mice, Knockout, Leptin, Mice, Agouti-Related Protein, Receptors, Leptin

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