Cited by 1,161Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyRegulation of Appetite and Obesity

A role for kisspeptins in the regulation of gonadotropin secretion in the mouse

Gottsch, M. L., Cunningham, M. J., Smith, J. T., Popa, S. M., Acohido, B. V., Crowley, W. F., Seminara, S., Clifton, D. K. +1 more·2004·Endocrinology

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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Crossref · 10.1210/en.2004-0431

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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
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

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