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Neurokinin B Stimulates GnRH Release in the Male Monkey (Macaca mulatta) and Is Colocalized with Kisspeptin in the Arcuate Nucleus
Open accessAbstract
Human genetics indicate that kisspeptin and neurokinin B (NKB) signaling are necessary for generating pulsatile LH release and therefore for initiation of puberty and maintaining gonadal function. In the present study, male monkeys were employed to examine 1) whether activation of the NKB receptor (NK3R) is associated with GnRH release, and 2) hypothalamic localization of these peptides using immunofluorescence histochemistry. Agonadal juveniles, in which pituitary responsiveness to GnRH was heightened by GnRH priming, were employed to indirectly examine GnRH-releasing actions of NK3R and kisspeptin receptor agonists by tracking LH after their i.v. injection. Castrated adults were used for immunohistochemistry. Single i.v. injections of NKB or senktide (an NK3R agonist) elicited robust LH discharges that were abolished by GnRH receptor antagonism (acyline) confirming the ligands' hypothalamic action. Intermittent infusion of senktide (1-min pulse every hour for 4 h), in contrast to that of kisspeptin, failed to sustain pulsatile GnRH release. Repetitive senktide injections did not compromise the GnRH-releasing action of kisspeptin. NKB and kisspeptin were colocalized in perikarya of the arcuate nucleus and in axonal projections to the median eminence, confirming earlier findings in sheep. These results are consistent with the human genetics, and indicate that although brief activation of NK3R stimulates GnRH release, repetitive stimulation of this pathway, in contrast to that of kisspeptin receptor, fails to sustain pulsatile GnRH release. In addition, the data provide a platform for future elucidation of the interactions between NKB and kisspeptin that are required for generating pulsatile GnRH release in primates.
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“Although the effect of NKB on GnRH secretion depends on the hormonal context, administration of NKB has been shown to elicit strong stimulation of LH production mediated by GnRH in animal models.64”
From Pubertal development and regulation (2016) · cites this paper as [64]
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Metadata
- Authors
- Ramaswamy, S., Seminara, S. B., Ali, B., Ciofi, P., Amin, N. A., & Plant, T. M.
- Affiliations
- University of Pittsburgh (US)
- Massachusetts General Hospital (US)
- Université de Bordeaux (FR)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2010-07-23
- Volume
- 151
- Issue
- 9
- Pages
- 4494-4503
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2940495
- OpenAlex
- W1972602091
- Cited by
- 267
- References
- 30
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 18 · 2020: 13 · 2019: 19 · 2018: 17 · 2017: 10 · 2016: 17 · 2015: 18 · 2014: 29 · 2013: 23 · 2012: 34
- FWCI
- 33.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD008610, P30HD008610, U54HD08610, R01-HD-13254, U54HD028138, R01HD013254)
- 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 › Neuroendocrine regulation and behavior
- Keywords
- neurokinin B, kisspeptin, GnRH release, NK3 receptor, senktide, pulsatile LH secretion, arcuate nucleus, hypothalamus, kisspeptin receptor, acyline, puberty, gonadotropin-releasing hormone, rhesus monkeys
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Drug Interactions, Humans, Immunohistochemistry, Injections, Intravenous, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Macaca mulatta, Male, Oligopeptides, Orchiectomy, Peptide Fragments, Quinolines, Receptors, LHRH, Substance P, Neurokinin B, Receptors, Neurokinin-3, Microscopy, Confocal, Receptors, G-Protein-Coupled, Kisspeptins
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