Cited by 238Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyReproductive Biology and Fertility

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Menopause and the human hypothalamus: Evidence for the role of kisspeptin/neurokinin B neurons in the regulation of estrogen negative feedback

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Rance, Naomi E.·2009·Peptides

DOI 10.1016/j.peptides.2008.05.016PMC PMC2632595

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Abstract

Menopause is characterized by depletion of ovarian follicles, a reduction of ovarian hormones to castrate levels and elevated levels of serum gonadotropins. Rather than degenerating, the reproductive neuroendocrine axis in postmenopausal women is intact and responds robustly to the removal of ovarian hormones. Studies in both human and non-human primates provide evidence that the gonadotropin hypersecretion in postmenopausal women is secondary to increased gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. In addition, menopause is accompanied by hypertrophy of neurons in the infundibular (arcuate) nucleus expressing KiSS-1, neurokinin B (NKB), substance P, dynorphin and estrogen receptor alpha (ERalpha) mRNA. Ovariectomy in experimental animals induces nearly identical findings, providing evidence that these changes are a compensatory response to ovarian failure. The anatomical site of the hypertrophied neurons, as well as the extensive data implicating kisspeptin, NKB and dynorphin in the regulation of GnRH secretion, provide compelling evidence that these neurons are part of the neural network responsible for the increased levels of serum gonadotropins in postmenopausal women. We propose that neurons expressing KiSS-1, NKB, substance P, dynorphin and ERalpha mRNA in the infundibular nucleus play an important role in sex-steroid feedback on gonadotropin secretion in the human.

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Research works printed but not linked: 4

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Authors: Rance, N. E.
Affiliations: University of Arizona (US)
Corresponding author: Rance, Naomi E.
ORCID: Rance, Naomi E.
Venue: Peptides
Publisher: Elsevier BV
Published: 2009-01
Volume: 30
Issue: 1
Pages: 111-122
ISSN: 0196-9781 (ISSN-L)
DOI: 10.1016/j.peptides.2008.05.016
PMC: PMC2632595
OpenAlex: W2092614270
Cited by: 237
References: 114
Citations by year: 2026: 4 · 2025: 11 · 2024: 15 · 2023: 4 · 2022: 7 · 2021: 11 · 2020: 6 · 2019: 10 · 2018: 12 · 2017: 12 · 2016: 12 · 2015: 17 · 2014: 18 · 2013: 21 · 2012: 18
FWCI: 22.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Peptides (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (AG09214, R56AG009214, R01AG009214)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
Keywords: menopause, hypothalamus, kisspeptin, neurokinin B, estrogen negative feedback, gonadotropin secretion, gonadotropin-releasing hormone, arcuate nucleus, ovariectomy, estrogen receptor alpha, dynorphin, substance P, postmenopausal women, ovarian failure
MeSH terms: Aging, Animals, Dynorphins, Estrogens, Female, Humans, Hypothalamus, Menopause, Middle Aged, Neurons, Neurosecretory Systems, Ovary, Substance P, Neurokinin B, Feedback, Physiological, Tumor Suppressor Proteins, Rats, Kisspeptins

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Menopause and the human hypothalamus: Evidence for the role of kisspeptin/neurokinin B neurons in the regulation of estrogen negative feedback

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