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Cited by 100Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyRegulation of Appetite and Obesity

Kisspeptin administration to women: a window into endogenous kisspeptin secretion and GnRH responsiveness across the menstrual cycle

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Chan, Yee-Ming, Butler, James P., Sidhoum, Valerie F., Pinnell, Nancy E., Seminara, Stephanie B.·2012·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2012-1282PMC PMC3410261
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Abstract

CONTEXT: Kisspeptin is the most powerful known stimulus of GnRH-induced LH secretion across mammalian species. However, the effects of kisspeptin are just being explored, and the dynamics of kisspeptin responsiveness across the menstrual cycle are incompletely understood. OBJECTIVE: The objective of the study was to characterize the effects of kisspeptin on GnRH secretion in healthy women in different phases of the menstrual cycle. PARTICIPANTS AND INTERVENTION: Ten women in the early follicular phase, three women in the late follicular (preovulatory) phase, and 14 women in the midluteal phase received a bolus of kisspeptin 112-121 0.24 nmol/kg iv. An additional four women in the early to midfollicular phase received kisspeptin 112-121 0.72 nmol/kg iv. RESULTS: The response to kisspeptin varied depending on the phase of the menstrual cycle. LH pulses were observed immediately after kisspeptin administration in all luteal and preovulatory women. However, only half the women in the early follicular phase had unambiguous kisspeptin responses. Increasing the kisspeptin dose did not increase the LH response in early to midfollicular phase women. Kisspeptin did not appear to reset the GnRH pulse generator in women as it does in men. CONCLUSIONS: Differences in responses to exogenous kisspeptin across the menstrual cycle suggest that kisspeptin tone is higher in the early follicular phase compared with other cycle phases. The mechanisms that determine the timing of GnRH pulse generation in men and women appear to be distinct.

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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 [32]

    The Methods report a single kisspeptin bolus in healthy women, and the early-follicular Results report increased mean LH afterward. The cited paper does not establish the claimed effect of hourly boluses on LH pulse frequency in 11 hyperprolactinemic women, nor does the identified passage describe the dose as physiologic. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The mean LH amplitude in response to the first kisspeptin IVB in hyperprolactinemic women was comparable to that observed in normoprolactinemic female volunteers in the midluteal phase.

    “Moreover, the mean LH amplitude in response to the first kisspeptin IVB in hyperprolactinemic women was comparable to that observed in normoprolactinemic female volunteers in the midluteal phase (32).”

    From Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans (2022) · cites this paper as [32]

  • This mean estradiol value is comparable to the estradiol levels observed in healthy volunteers in the early follicular phase of the menstrual cycle undergoing a similar protocol (35 ± 3 pg/mL).

    “This value is comparable to the estradiol levels observed in healthy volunteers in the early follicular phase of the menstrual cycle undergoing a similar protocol (35 ± 3 pg/mL) (32).”

    From Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans (2022) · cites this paper as [32]

  • 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 [56]

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Authors
Chan, Y.-M., Butler, J. P., Sidhoum, V. F., Pinnell, N. E., & Seminara, S. B.
Affiliations
  • Harvard University (US)
  • Brigham and Women's Hospital (US)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2012-08
Volume
97
Issue
8
Pages
E1458-E1467
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2012-1282
PMC
PMC3410261
OpenAlex
W2076309282
Cited by
100
References
47
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 8 · 2016: 10 · 2015: 13 · 2014: 13 · 2013: 8 · 2012: 3
FWCI
13.78
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Massachusetts General Hospital
  • Harvard University
  • Harvard Catalyst
  • National Institutes of Health
  • National Center for Research Resources (UL1RR025758)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD43341, R01HD043341, K24HD067388)
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 secretion, luteinizing hormone, menstrual cycle, follicular phase, luteal phase, GnRH pulse generator, LH pulsatility
MeSH terms
Adult, Female, Humans, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Menstrual Cycle, Young Adult, Kisspeptins

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