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

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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., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M.·2005·Endocrinology

DOI 10.1210/en.2004-0836

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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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Background
The Metastasis Suppressor Gene KiSS-1 Encodes Kisspeptins, the Natural Ligands of the Orphan G Protein-coupled Receptor GPR54
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The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system
Funes, S., Hedrick, J. A., Vassileva, G., Markowitz, L., Abbondanzo, S., Golovko, A., Yang, S., Monsma, F. J., & Gustafson, E. L. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.066 · Cited by 675

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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
ORCID: Navarro, V. M.
Castellano, J. M.
Tovar, S.
Roa, J.
Nogueiras, R.
Magni, P.
Aguilar, E.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2005-01-01
Volume: 146
Issue: 1
Pages: 156-163
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2004-0836
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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Characterization of the Potent Luteinizing Hormone-Releasing Activity of KiSS-1 Peptide, the Natural Ligand of GPR54

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