Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men
Open accessAbstract
CONTEXT: Kisspeptins stimulate GnRH and thus gonadotropin secretion. Kisspeptin-10 is the minimal kisspeptin sequence with full intrinsic bioactivity, but it has not been studied in man. OBJECTIVE: We investigated our hypothesis that kisspeptin-10 increases GnRH and thus LH pulse frequency. DESIGN AND PARTICIPANTS: The dose response of kisspeptin-10 was investigated by administering iv bolus doses (0.01-3.0 μg/kg) and vehicle to healthy men. Effects on LH pulse frequency and size were determined by deconvolution analysis during infusion of kisspeptin-10 for up to 22.5 h. RESULTS: Intravenous bolus kisspeptin-10 resulted in a rapid and dose-dependent rise in serum LH concentration, with maximal stimulation at 1 μg/kg (4.1 ± 0.4 to 12.4 ± 1.7 IU/liter at 30 min, P < 0.001, n = 6). Administration of 3 μg/kg elicited a reduced response vs. 1 μg/kg (P < 0.05). Infusion of kisspeptin-10 at 4 μg/kg · h for 22.5 h elicited an increase in LH from a mean of 5.4 ± 0.7 to 20.8 ± 4.9 IU/liter (n = 4; P < 0.05) and serum testosterone increased from 16.6 ± 2.4 to 24.0 ± 2.5 nmol/liter (P < 0.001). LH pulses were obscured at this high rate of secretion, but a lower dose infusion of kisspeptin-10 (1.5 μg/kg · h) increased mean LH from 5.2 ± 0.8 to 14.1 ± 1.7 IU/liter (n = 4; P < 0.01) and increased LH pulse frequency from 0.7 ± 0.1 to 1.0 ± 0.2 pulses/h (P < 0.05) and secretory burst mass from 3.9 ± 0.4 to 12.8 ± 2.6 IU/liter (P < 0.05). CONCLUSIONS: Kisspeptin-10 boluses potently evoke LH secretion in men, and continuous infusion increases testosterone, LH pulse frequency, and pulse size. Kisspeptin analogues have therapeutic potential as regulators of LH and thus testosterone secretion.
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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 [55]
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References 47 · Cited by 186
- Authors
- George, J. T., Veldhuis, J. D., Roseweir, A. K., Newton, C. L., Faccenda, E., Millar, R. P., & Anderson, R. A.
- Affiliations
- The Queen's Medical Research Institute (GB)
- Mayo Clinic (US)
- University of Cape Town (ZA)
- Corresponding author
- George, J. T.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2011-08
- Volume
- 96
- Issue
- 8
- Pages
- E1228-E1236
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3380939
- OpenAlex
- W2128786502
- Cited by
- 186
- References
- 47
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 5 · 2022: 10 · 2021: 11 · 2020: 12 · 2019: 7 · 2018: 19 · 2017: 16 · 2016: 11 · 2015: 14 · 2014: 20 · 2013: 13 · 2012: 17
- FWCI
- 18.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- UpSpace Institutional Repository (University of Pretoria) (submittedVersion)
- Funders
- Wellcome Trust
- Medical Research Council (G0701682)
- National Institute on Aging (R01AG031763)
- 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-10, luteinizing hormone secretion, LH pulse frequency, gonadotropin-releasing hormone, gonadotropin secretion, testosterone, dose-response relationship, pulsatile LH secretion, men, kisspeptin receptor, hypothalamic-pituitary-gonadal axis
- MeSH terms
- Adult, Dose-Response Relationship, Drug, Follicle Stimulating Hormone, Humans, Hypothalamo-Hypophyseal System, Injections, Intravenous, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Tachyphylaxis, Testosterone, Tumor Suppressor Proteins, Kisspeptins
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