A role for kisspeptins in the regulation of gonadotropin secretion in the mouse
Abstract
Kisspeptins are products of the KiSS-1 gene, which bind to a G protein-coupled receptor known as GPR54. Mutations or targeted disruptions in the GPR54 gene cause hypogonadotropic hypogonadism in humans and mice, suggesting that kisspeptin signaling may be important for the regulation of gonadotropin secretion. To examine the effects of kisspeptin-54 (metastin) and kisspeptin-10 (the biologically active C-terminal decapeptide) on gonadotropin secretion in the mouse, we administered the kisspeptins directly into the lateral cerebral ventricle of the brain and demonstrated that both peptides stimulate LH secretion. Further characterization of kisspeptin-54 demonstrated that it stimulated both LH and FSH secretion, at doses as low as 1 fmol; moreover, this effect was shown to be blocked by pretreatment with acyline, a potent GnRH antagonist. To learn more about the functional anatomy of kisspeptins, we mapped the distribution of KiSS-1 mRNA in the hypothalamus. We observed that KiSS-1 mRNA is expressed in areas of the hypothalamus implicated in the neuroendocrine regulation of gonadotropin secretion, including the anteroventral periventricular nucleus, the periventricular nucleus, and the arcuate nucleus. We conclude that kisspeptin-GPR54 signaling may be part of the hypothalamic circuitry that governs the hypothalamic secretion of GnRH.
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- Authors
- Gottsch, M. L., Cunningham, M. J., Smith, J. T., Popa, S. M., Acohido, B. V., Crowley, W. F., Seminara, S., Clifton, D. K., & Steiner, R. A.
- Affiliations
- University of Washington (US)
- Harvard University (US)
- Corresponding author
- Steiner, R. A.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2004-09-01
- Volume
- 145
- Issue
- 9
- Pages
- 4073-4077
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2028777780
- Cited by
- 1,161
- References
- 28
- Citations by year
- 2026: 9 · 2025: 31 · 2024: 31 · 2023: 27 · 2022: 54 · 2021: 67 · 2020: 46 · 2019: 39 · 2018: 55 · 2017: 52 · 2016: 63 · 2015: 52 · 2014: 78 · 2013: 85 · 2012: 80
- FWCI
- 38.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- ResearchWorks at the University of Washington (University of Washington) (submittedVersion)
- Funders
- National Science Foundation (0110686)
- Massachusetts General Hospital
- Northwestern University
- National Institutes of Health (5u54hd012629-31)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061517, R01 DK61517)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 27142, R01HD015788, U54-HD-12629, U54HD029164, U54HD28138, R01HD027142, U54HD028138)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- kisspeptin, KISS1, GPR54, kisspeptin-54, kisspeptin-10, gonadotropin secretion, luteinizing hormone, follicle-stimulating hormone, gonadotropin-releasing hormone, hypothalamus, arcuate nucleus, periventricular nucleus, hypogonadotropic hypogonadism, acyline, GnRH antagonist, neuroendocrine regulation of reproduction
- MeSH terms
- Receptors, Kisspeptin-1, Animals, Hypothalamus, Injections, Intraventricular, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Mice, Inbred C57BL, Proteins, RNA, Messenger, Receptors, Neuropeptide, Receptors, G-Protein-Coupled, Mice, Kisspeptins
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 ›
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