Kisspeptin resets the hypothalamic GnRH clock in men

Chan, Yee-Ming; Butler, James P.; Pinnell, Nancy E.; Pralong, François P.; Crowley, William F.; Ren, Chen; Chan, Kenneth K.; Seminara, Stephanie B.

doi:10.1210/jc.2010-3046

Cited by 115Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyRegulation of Appetite and Obesity

Kisspeptin resets the hypothalamic GnRH clock in men

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Chan, Yee-Ming, Butler, James P., Pinnell, Nancy E., Pralong, François P., Crowley, William F., Ren, Chen, Chan, Kenneth K., Seminara, Stephanie B.·2011·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2010-3046PMC PMC3100758

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Abstract

Context: Reproduction in all mammals is controlled by a hypothalamic clock that produces periodic secretory pulses of GnRH, but how the timing of these pulses is determined is poorly understood. The neuropeptide kisspeptin potently and selectively stimulates the secretion of GnRH. Although this property of kisspeptin is well described, the effects of kisspeptin on endogenous GnRH pulse generation remain largely unexplored. Objective: The objective of the study was to detail the effects of kisspeptin on GnRH secretion, as reflected by LH secretion, in men. Participants: Thirteen healthy adult men participated in the study. Intervention: The intervention was the administration of a single iv bolus of the C-terminal decapeptide of kisspeptin (amino acids 112–121 of the parent protein). Results: Kisspeptin induced an immediate LH pulse, regardless of the timing of the previous endogenous pulse. The kisspeptin-induced pulses were on average larger than endogenous pulses (amplitude 5.0 ± 1.0 vs. 2.1 ± 0.3 mIU/ml, P = 0.02). Comparison of the morphology of kisspeptin-induced LH pulses in healthy men with that of GnRH-induced LH pulses in men with isolated GnRH deficiency suggests that a single iv bolus of kisspeptin triggered sustained GnRH release lasting approximately 17 min. Furthermore, kisspeptin reset the GnRH pulse generator, as it not only induced an immediate LH pulse but also delayed the next endogenous pulse by an interval approximating the normal interpulse interval. Conclusions: As the first known agent capable of resetting the hypothalamic GnRH pulse generator, kisspeptin can be used as a physiological tool for studying GnRH pulse generation and opens a door to understanding the mechanisms of biological clocks in general.

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Repetitive bolus administration of kisspeptin at a physiologic dose and at a frequency of 1 bolus/hour increased mean LH levels and LH pulse frequency in the entire cohort (n = 11) of hyperprolactinemic women.
“Repetitive bolus administration of kisspeptin at a physiologic dose (30, 32) and at a frequency of 1 bolus/hour increased mean LH levels and LH pulse frequency in the entire cohort (n = 11) of hyperprolactinemic women.”
From Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans (2022) · cites this paper as [30]

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Authors: Chan, Y.-M., Butler, J. P., Pinnell, N. E., Pralong, F. P., Crowley, W. F., Ren, C., Chan, K. K., & Seminara, S. B.
Affiliations: Brigham and Women's Hospital (US)
Harvard University (US)
The Ohio State University (US)
ORCID: Chan, Yee-Ming
Butler, James P.
Pralong, François P.
Crowley, William F.
Ren, Chen
Seminara, Stephanie B.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2011-06-01
Volume: 96
Issue: 6
Pages: E908-E915
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2010-3046
PMC: PMC3100758
OpenAlex: W1989716417
Cited by: 114
References: 43
Citations by year: 2026: 3 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 9 · 2018: 12 · 2017: 5 · 2016: 8 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 13
FWCI: 14.34
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Massachusetts General Hospital
Harvard Catalyst
National Center for Research Resources (UL1RR025758)
NIH Clinical Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD015788, T32HD007396, R01 HD43341, R01HD043341, K24HD067388, U54HD028138)
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, GnRH pulse generator, GnRH secretion, luteinizing hormone secretion, GnRH deficiency, men, biological clock
MeSH terms: Adult, Analysis of Variance, Humans, Hypothalamus, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Periodicity, Tumor Suppressor Proteins, Kisspeptins

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Kisspeptin resets the hypothalamic GnRH clock in men

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