The kisspeptin system of the human hypothalamus: sexual dimorphism and relationship with gonadotropin‐releasing hormone and neurokinin B neurons
Abstract
Kisspeptin signaling via the kisspeptin receptor G‐protein‐coupled receptor‐54 plays a fundamental role in the onset of puberty and the regulation of mammalian reproduction. In this immunocytochemical study we addressed the (i) topography, (ii) sexual dimorphism, (iii) relationship to gonadotropin‐releasing hormone (GnRH) neurons and (iv) neurokinin B content of kisspeptin‐immunoreactive hypothalamic neurons in human autopsy samples. In females, kisspeptin‐immunoreactive axons formed a dense periventricular plexus and profusely innervated capillary vessels in the infundibular stalk. Most immunolabeled somata occurred in the infundibular nucleus. Many cells were also embedded in the periventricular fiber plexus. Rostrally, they formed a prominent periventricular cell mass (magnocellular paraventricular nucleus). Robust sex differences were noticed in that fibers and somata were significantly less numerous in male individuals. In dual‐immunolabeled specimens, fine kisspeptin‐immunoreactive axon varicosities formed axo‐somatic, axo‐dendritic and axo‐axonal contacts with GnRH neurons. Dual‐immunofluorescent studies established that 77% of kisspeptin‐immunoreactive cells in the infundibular nucleus synthesize the tachykinin peptide neurokinin B, which is known to play crucial role in human fertility; 56 and 17% of kisspeptin fibers in the infundibular and periventricular nuclei, respectively, contained neurokinin B immunoreactivity. Site‐specific co‐localization patterns implied that kisspeptin neurons in the infundibular nucleus and elsewhere contributed differentially to these plexuses. This study describes the distribution and robust sexual dimorphism of kisspeptin‐immunoreactive elements in human hypothalami, reveals neuronal contacts between kisspeptin‐immunoreactive fibers and GnRH cells, and demonstrates co‐synthesis of kisspeptins and neurokinin B in the infundibular nucleus. The neuroanatomical information will contribute to our understanding of central mechanisms whereby kisspeptins regulate human fertility.
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Kisspeptin is a neuropeptide involved in the regulation of reproductive function and also has a significant role in the regulation of glucose homeostasis, feeding behavior, and body composition.
“Kisspeptin is a neuropeptide involved in the regulation of reproductive function and also has a significant role in the regulation of glucose homeostasis, feeding behavior, and body composition [131].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [131]
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- Authors
- Hrabovszky, E., Ciofi, P., Vida, B., Horvath, M. C., Keller, E., Caraty, A., Bloom, S. R., Ghatei, M. A., Dhillo, W. S., Liposits, Z., & Kallo, I.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Hammersmith Hospital (GB)
- Pázmány Péter Catholic University (HU)
- Corresponding author
- Hrabovszky, E.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2010-06
- Volume
- 31
- Issue
- 11
- Pages
- 1984-1998
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2100978216
- Cited by
- 314
- References
- 53
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 13 · 2023: 12 · 2022: 23 · 2021: 29 · 2020: 17 · 2019: 21 · 2018: 24 · 2017: 17 · 2016: 22 · 2015: 25 · 2014: 26 · 2013: 30 · 2012: 20
- FWCI
- 24.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Science Foundation
- National Institute for Health and Care Research (NF-SI-0507-10337)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- kisspeptin, human hypothalamus, sexual dimorphism, GnRH neurons, neurokinin B, arcuate nucleus, human fertility, puberty onset, neuroanatomy
- MeSH terms
- Adult, Aged, Animals, Female, Humans, Hypothalamus, Gonadotropin-Releasing Hormone, Male, Middle Aged, Neurons, Protein Precursors, Puberty, Reproduction, Sex Characteristics, Neurokinin B, Signal Transduction, Tumor Suppressor Proteins, Kisspeptins
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