Cited by 449Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyRegulation of Appetite and Obesity

Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54

Navarro, V. M., Castellano, J. M., Fernández-Fernández, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J. +6 more·2005·Endocrinology

Abstract

Loss-of-function mutations of the gene encoding GPR54, the putative receptor for the KiSS-1-derived peptide metastin, have been recently associated with hypogonadotropic hypogonadism, in both rodents and humans. Yet the actual role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion remains largely unexplored. To initiate such analysis, the effects of KiSS-1 peptide on LH secretion were monitored using in vivo and in vitro settings under different experimental conditions. Central intracerebroventricular administration of KiSS-1 peptide potently elicited LH secretion in vivo over a range of doses from 10 pmol to 1 nmol. The effect of centrally injected KiSS-1 appeared to be mediated via the hypothalamic LHRH. However, no effect of central administration of KiSS-1 was detected on relative LHRH mRNA levels. Likewise, systemic (ip and iv) injection of KiSS-1 markedly stimulated LH secretion. This effect was similar in terms of maximum response to that of central administration of KiSS-1 and might be partially attributed to its ability to stimulate LH secretion directly at the pituitary. Finally, the LH-releasing activity of KiSS-1 was persistently observed after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e. relevant neurotransmitters in the neuroendocrine control of LH secretion. In summary, our results provide solid evidence for a potent stimulatory effect of KiSS-1 on LH release, acting at central levels (likely the hypothalamus) and eventually at the pituitary, and further document a novel role of the KiSS-1/GPR54 system as a relevant downstream element in the neuroendocrine network governing LH secretion.

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Crossref · 10.1210/en.2004-0836

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  • Kisspeptin has been reported not to affect circulating levels of PRL in adult rats, ewes, rhesus monkeys, or healthy women.

    “Kisspeptin has been reported not to affect circulating levels of PRL in adult rats (38), ewes (39), rhesus monkeys (40), or healthy women (41).”

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Authors
Navarro, V. M., Castellano, J. M., Fernández-Fernández, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., & Tena-Sempere, M.
Affiliations
  • University of Córdoba (ES)
  • Universidade de Santiago de Compostela (ES)
  • University of Milan (IT)
  • Department of Physiology (S.T., R.N., M.J.V., C.D.), University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
  • Department of Cell Biology, Physiology and Immunology (V.M.N., J.M.C., R.F.-F., J.R., A.M., M.L.B., E.A., L.P., M.T.-S.), University of Córdoba, 14004 Córdoba, Spain
Venue
Endocrinology
Published
2005-01-01
Volume
146
Issue
1
Pages
156-163
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2141217442
Cited by
449
References
35
Citations by year
2026: 3 · 2025: 2 · 2024: 8 · 2023: 11 · 2022: 21 · 2021: 16 · 2020: 16 · 2019: 16 · 2018: 15 · 2017: 12 · 2016: 22 · 2015: 18 · 2014: 19 · 2013: 26 · 2012: 22
FWCI
31.04
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
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
KISS1, kisspeptin, GPR54, luteinizing hormone secretion, excitatory amino acids, nitric oxide, hypogonadotropic hypogonadism
MeSH terms
Receptors, Kisspeptin-1, Animals, Dose-Response Relationship, Drug, Drug Interactions, Injections, Intraperitoneal, Injections, Intravenous, Injections, Intraventricular, Luteinizing Hormone, Ligands, Nitric Oxide, Pituitary Gland, Proteins, Rats, Wistar, Receptors, Neuropeptide, Excitatory Amino Acids, Receptors, G-Protein-Coupled, Mice, Rats, Kisspeptins

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