Substance P immunoreactivity exhibits frequent colocalization with kisspeptin and neurokinin B in the human infundibular region
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Neurons synthesizing neurokinin B (NKB) and kisspeptin (KP) in the hypothalamic arcuate nucleus represent important upstream regulators of pulsatile gonadotropin-releasing hormone (GnRH) neurosecretion. In search of neuropeptides co-expressed in analogous neurons of the human infundibular nucleus (Inf), we have carried out immunohistochemical studies of the tachykinin peptide Substance P (SP) in autopsy samples from men (21-78 years) and postmenopausal (53-83 years) women. Significantly higher numbers of SP-immunoreactive (IR) neurons and darker labeling were observed in the Inf of postmenopausal women than in age-matched men. Triple-immunofluorescent studies localized SP immunoreactivity to considerable subsets of KP-IR and NKB-IR axons and perikarya in the infundibular region. In postmenopausal women, 25.1% of NKB-IR and 30.6% of KP-IR perikarya contained SP and 16.5% of all immunolabeled cell bodies were triple-labeled. Triple-, double- and single-labeled SP-IR axons innervated densely the portal capillaries of the infundibular stalk. In quadruple-labeled sections, these axons formed occasional contacts with GnRH-IR axons. Presence of SP in NKB and KP neurons increases the functional complexity of the putative pulse generator network. First, it is possible that SP modulates the effects of KP and NKB in axo-somatic and axo-dendritic afferents to GnRH neurons. Intrinsic SP may also affect the activity and/or neuropeptide release of NKB and KP neurons via autocrine/paracrine actions. In the infundibular stalk, SP may influence the KP and NKB secretory output via additional autocrine/paracrine mechanisms or regulate GnRH neurosecretion directly. Finally, possible co-release of SP with KP and NKB into the portal circulation could underlie further actions on adenohypophysial gonadotrophs.
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Neurons co-expressing kisspeptin and NKB in the human mediobasal hypothalamus often co-express substance P.
“Neurons co-expressing kisspeptin and NKB in the human mediobasal hypothalamus often co-express substance P.65”
From Pubertal development and regulation (2016) · cites this paper as [65]
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- Authors
- Hrabovszky, E., Borsay, B. Á., Rácz, K., Herczeg, L., Ciofi, P., Bloom, S. R., Ghatei, M. A., Dhillo, W. S., & Liposits, Z.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- University of Debrecen (HU)
- Inserm (FR)
- Hammersmith Hospital (GB)
- Pázmány Péter Catholic University (HU)
- Corresponding author
- Hrabovszky, Erik
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-08-19
- Volume
- 8
- Issue
- 8
- Pages
- e72369
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3747144
- OpenAlex
- W2040816452
- Cited by
- 57
- References
- 44
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 5 · 2013: 2
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- National Science Foundation (FP7/2007-2013)
- National Institute for Health and Care Research (CDF-2009-02-05)
- European Commission (245009)
- Hungarian Scientific Research Fund (K83710, K100722)
- 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
- substance P, kisspeptin, neurokinin B, arcuate nucleus, gonadotropin-releasing hormone, pulsatile GnRH secretion, postmenopausal women, hypothalamic-pituitary-gonadal axis, neuropeptide co-localization, autocrine and paracrine signaling, gonadotrophs, tachykinins
- MeSH terms
- Adult, Aged, Aged, 80 and over, Arcuate Nucleus of Hypothalamus, Axons, Capillaries, Female, Fluorescent Antibody Technique, Humans, Gonadotropin-Releasing Hormone, Male, Middle Aged, Pituitary Gland, Substance P, Neurokinin B, Protein Transport, Young Adult, Kisspeptins, Cell Body
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