Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54
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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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).”
From Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans (2022) · cites this paper as [38]
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Self-citation
- 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
- Publisher
- The Endocrine Society
- 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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