Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males
Abstract
CONTEXT: Mutation of the G protein-coupled receptor 54 is associated with a failure of reproductive function. The endogenous neuropeptide agonist for G protein-coupled receptor 54, kisspeptin, potently stimulates the hypothalamic-pituitary-gonadal axis in rodents and primates. OBJECTIVE: The present study was designed to determine the effects of elevating circulating kisspeptin levels on LH, FSH, and testosterone in male volunteers. DESIGN: This was a double-blind, placebo-controlled, crossover study. SETTING: This was a hospital-based study. PARTICIPANTS: Male volunteers (n = 6) were recruited. INTERVENTIONS: Each volunteer received a 90-min i.v. infusion of kisspeptin-54 (4 pmol/kg x min) and a control infusion of saline (0.9%) in random order. MAIN OUTCOME MEASURE: Plasma LH, FSH, and testosterone concentrations were measured. RESULTS: Kisspeptin-54 infusion significantly increased plasma LH, FSH, and testosterone concentrations compared with saline infusion (mean 90-min LH: kisspeptin, 10.8 +/- 1.5 vs. saline, 4.2 +/- 0.5 U/liter, P < 0.001; mean 90-min FSH: kisspeptin, 3.9 +/- 0.7 vs. saline, 3.2 +/- 0.6 U/liter, P < 0.001; mean 180-min testosterone: kisspeptin, 24.9 +/- 1.7 vs. saline, 21.7 +/- 2.2 nmol/liter, P < 0.001). The plasma half-life of kisspeptin-54 was calculated to be 27.6 +/- 1.1 min. The mean metabolic clearance rate was 3.2 +/- 0.2 ml/kg x min, and the volume of distribution was 128.9 +/- 12.5 ml/kg. CONCLUSION: Elevation of plasma concentrations of kisspeptin in human males significantly increases circulating LH, FSH, and testosterone levels. Kisspeptin infusion provides a novel mechanism for hypothalamic-pituitary-gonadal axis manipulation in disorders of the reproductive system.
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Administration of kisspeptin results in increases in plasma LH concentrations in healthy men, and in women kisspeptin also induces LH release, although the response varies across the menstrual cycle.
“Administration of kisspeptin results in increases in plasma LH concentrations in healthy men,54,55 and in women kisspeptin also induces LH release, although the response varies across the menstrual cycle.56”
From Pubertal development and regulation (2016) · cites this paper as [54]
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- Authors
- Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., & Bloom, S. R.
- Affiliations
- Imperial College London (GB)
- Hammersmith Hospital (GB)
- Corresponding author
- Bloom, Stephen R.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-12
- Volume
- 90
- Issue
- 12
- Pages
- 6609-6615
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2120568375
- Cited by
- 656
- References
- 33
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 15 · 2023: 28 · 2022: 28 · 2021: 35 · 2020: 27 · 2019: 31 · 2018: 36 · 2017: 28 · 2016: 35 · 2015: 41 · 2014: 38 · 2013: 36 · 2012: 47
- FWCI
- 34.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust
- Imperial College London
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- 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-54, kisspeptin, hypothalamic-pituitary-gonadal axis, luteinizing hormone, follicle-stimulating hormone, testosterone, male reproductive function
- MeSH terms
- Receptors, Kisspeptin-1, Adult, Dose-Response Relationship, Drug, Follicle Stimulating Hormone, Half-Life, Humans, Hypothalamo-Hypophyseal System, Infusions, Intravenous, Luteinizing Hormone, Male, Osmolar Concentration, Pituitary-Adrenal System, Proteins, Testosterone, Time Factors, Receptors, Neuropeptide, Cross-Over Studies, Tumor Suppressor Proteins, Receptors, G-Protein-Coupled, Kisspeptins
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