Cited by 53Hypothalamic control of reproductive hormonesStress Responses and CortisolNeuropeptides and Animal Physiology

Stress Increases Gonadotropin Inhibitory Hormone Cell Activity and Input to GnRH Cells in Ewes

Open access
Clarke, Iain J., Bartolini, Danielle, Conductier, Gregory, Henry, Belinda A.·2016·Endocrinology

Abstract

Stress reduces GnRH and gonadotropin secretion in sheep, but the central mechanism for this suppressive effect is unknown. Gonadotropin-inhibitory hormone (GnIH) negatively regulates GnRH neurons and gonadotropes. Here, we measured activity of GnIH neurons and contact of GnIH fibers on GnRH neurons during either chronic "pseudostress" or acute stress in sheep. We also measured GnIH secretion into hypophysial portal blood during pseudostress and acute stress. The pseudostress was daily im injections (0.5 mg) of Synacthen Depot (adrenocorticotropin) or vehicle for 4 weeks, which increased the GnIH cell number and gene expression/cell in the hypothalamus, measured by in situ hybridization. Double label immunohistochemistry showed that Synacthen Depot treatment increased the percentage of GnRH cells in close contact with GnIH fibers but did not alter GnIH levels in hypophysial portal blood. Acute stress protocols were either sequential audiovisual predator stress, followed by insulin-induced hypoglycemia, or a single challenge with lipopolysaccharide (iv). Both of these acute stressors activated a c-Fos response in GnIH cells and increased the contacts of GnIH fibers to GnRH cells. Neither acute stress protocol increased GnIH secretion into hypophysial portal blood. These data show that chronic pseudostress and acute stressors increase the function of GnIH cells as well as the degree to which GnIH cells may provide input to GnRH cells. Thus, GnIH cells may provide a central mechanism whereby stress compromises reproduction. Neither chronic pseudostress nor acute stress elevates secretion of GnIH into portal blood, but stress effects mediated by GnIH cells are directed towards GnRH cell bodies.

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.2016-1513

Cites

46 of 46 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?

  • These effects are mediated through suppression of GnRH and GnRHR synthesis, disruption in pituitary release of LH, and enhanced function of GnIH neurons.

    “These effects are mediated through suppression of GnRH and GnRH receptor (GnRHR) synthesis, disruption in pituitary release of LH, and enhanced function of the gonadotropin-inhibitory hormone (GnIH; mammalian ortholog gene Rfrp3) neurons [21,23,24,25].”

    From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [21]

    The Discussion (page not provided) links stress-induced GnIH cell activation and increased contact with GnRH cells to reduced GnRH and gonadotropin secretion. It does not establish suppression of GnRH or GnRHR synthesis, or demonstrate that stress disrupts LH release directly at the pituitary. (LLM, conf=0.87)

    Experimental — accuracy not yet measured
  • Stress-mediated inhibition of GnRH release has been demonstrated in several species, including fish, birds, rodents, livestock, and humans.

    “Stress-mediated inhibition of GnRH release has been demonstrated in several species, including fish, birds, rodents, livestock, and humans [20,21,22].”

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

Research works printed but not linked: 1

  1. [33]33. Williams CY, Harris TG, Battaglia DF, Viguié C, Karsch FJ. Endo- toxin inhibits pituitary responsiveness to gonadotropin-releasing hormone. Endocrinology. 2001;142:1915-1922.

Cited by

Sorted by citations

Authors
Clarke, I. J., Bartolini, D., Conductier, G., & Henry, B. A.
Affiliations
Monash University (AU)
Corresponding author
Clarke, Iain J.
Venue
Endocrinology
Published
2016-11
Volume
157
Issue
11
Pages
4339-4350
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2511970244
Cited by
45
References
46
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 8
FWCI
8.42
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Monash University
  • Medical Research Council
  • National Health and Medical Research Council
  • National Medical Research Council
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
gonadotropin-inhibitory hormone, GnRH neurons, stress, sheep, hypothalamus, ACTH, predator stress, insulin-induced hypoglycemia, lipopolysaccharide, c-fos, hypophysial portal blood, reproduction, gonadotropin secretion
MeSH terms
Animals, Female, Gonadotropins, Hypothalamic Hormones, Hypothalamus, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Lipopolysaccharides, Neurons, Radioimmunoassay, Sheep, Stress, Physiological, In Situ Hybridization

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