Kisspeptin-neuron control of LH pulsatility and ovulation

Stevenson, Harvey; Bartram, Samuel; Charalambides, Mikaela Maria; Murthy, Sruthi; Petitt, Theo; Pradeep, Anjali; Vineall, Owen; Abaraonye, Ikenna; Lancaster, Amelia; Koysombat, Kanyada; Patel, Bijal; Abbara, Ali

doi:10.3389/fendo.2022.951938

Cited by 48Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyReproductive Biology and Fertility

Kisspeptin-neuron control of LH pulsatility and ovulation

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Stevenson, Harvey, Bartram, Samuel, Charalambides, Mikaela Maria, Murthy, Sruthi, Petitt, Theo, Pradeep, Anjali, Vineall, Owen, Abaraonye, Ikenna +4 more·2022·Frontiers in Endocrinology

DOI 10.3389/fendo.2022.951938PMC PMC9721495

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Abstract

Feedback from oestradiol (E2) plays a critical role in the regulation of major events in the physiological menstrual cycle including the release of gonadotrophins to stimulate follicular growth, and the mid-cycle luteinising hormone (LH) surge that leads to ovulation. E2 predominantly exerts its action via oestrogen receptor-alpha (ERα), however, as gonadotrophin releasing hormone (GnRH) neurons lack ERα, E2-feedback is posited to be indirectly mediated via upstream neurons. Kisspeptin (KP) is a neuropeptide expressed in hypothalamic KP-neurons that control GnRH secretion and plays a key role in the central mechanism regulating the hypothalamic-pituitary-gonadal (HPG) axis. In the rodent arcuate (ARC) nucleus, KP is co-expressed with Neurokinin B and Dynorphin; and thus, these neurons are termed ‘Kisspeptin-Neurokinin B-Dynorphin’ (KNDy) neurons. ARC KP-neurons function as the ‘GnRH pulse generator’ to regulate GnRH pulsatility, as well as mediating negative feedback from E2. A second KP neuronal population is present in the rostral periventricular area of the third ventricle (RP3V), which includes anteroventral periventricular (AVPV) nucleus and preoptic area neurons. These RP3V KP-neurons mediate positive feedback to induce the mid-cycle luteinising hormone (LH) surge and subsequent ovulation. Here, we describe the role of KP-neurons in these two regions in mediating this differential feedback from oestrogens. We conclude by considering reproductive diseases for which exploitation of these mechanisms could yield future therapies.

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Male rodents have lower kisspeptin neurons in the rostral periventricular area of the third ventricle, possibly explaining male inability to mount the estrogen-induced LH surge.
“Male rodents have lower kisspeptin neurons in the rostral periventricular area of the third ventricle, possibly explaining male inability to mount the estrogen-induced LH surge [99].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [99]
The section “Kisspeptin neurons in RP3V induce an LH surge to trigger ovulation” (page unavailable) says RP3V kisspeptin neurons mediate the estrogen-induced LH surge in rodents. It does not say that male rodents have fewer RP3V kisspeptin neurons or that this explains an inability to mount the surge; searches for male–female differences and male LH surges found no such passage. (LLM, conf=0.83)
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Authors: Stevenson, H., Bartram, S., Charalambides, M. M., Murthy, S., Petitt, T., Pradeep, A., Vineall, O., Abaraonye, I., Lancaster, A., Koysombat, K., Patel, B., & Abbara, A.
Affiliations: Imperial College London (GB)
Corresponding author: Abbara, Ali
ORCID: Stevenson, Harvey
Koysombat, Kanyada
Patel, Bijal
Abbara, Ali
Venue: Frontiers in Endocrinology
Publisher: Frontiers Media SA
Published: 2022-11-21
Volume: 13
Pages: 951938-951938
ISSN: 1664-2392 (ISSN-L)
DOI: 10.3389/fendo.2022.951938
PMC: PMC9721495
OpenAlex: W4309544083
Cited by: 48
References: 81
Citations by year: 2026: 7 · 2025: 15 · 2024: 19 · 2023: 7
FWCI: 1.65
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Endocrinology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Spiral (Imperial College London) (submittedVersion, other-oa)
Funders: National Institute for Health and Care Research (CS-2018, ACF‐2021‐21‐001, CS-2018-18-ST2-002)
Medical Research Council (CS-2018-18-ST2-002, MR/W024144/1)
NIHR Imperial Biomedical Research Centre
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 › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords: kisspeptin, ovulation, estrogen receptor alpha, GnRH neurons, hypothalamic-pituitary-gonadal axis, anteroventral periventricular nucleus, preoptic area, luteinizing hormone surge, reproductive disorders
MeSH terms: Dynorphins, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Neurons, Neurokinin B, Kisspeptins

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Kisspeptin-neuron control of LH pulsatility and ovulation

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