Coexpression of dynorphin and neurokinin B immunoreactivity in the rat hypothalamus: morphologic evidence of interrelated function within the arcuate nucleus
Abstract
Considerable evidence suggests that dynorphin and neurokinin B (NKB) neurons in the hypothalamic arcuate nucleus participate in the sex-steroid regulation of reproduction. In the present study, we used dual-label immunofluorescence to explore the distribution of prodynorphin and proNKB immunoreactivity in the rat hypothalamus. Additionally, we investigated whether arcuate prodynorphin-ir (immunoreactive) neurons expressed the neurokinin 3 receptor (NK3R) or nuclear estrogen receptor-alpha (ERalpha). We found that the majority of prodynorphin-ir neurons in the rat arcuate nucleus expressed proNKB, whereas nearly all (99%) of the proNKB neurons were immunoreactive for prodynorphin. The arcuate nucleus was the only site in the hypothalamus where neuronal somata coexpressing prodynorphin and proNKB-immunoreactivity were identified. A dense plexus of double-labeled prodynorphin/proNKB-ir fibers was found within the arcuate nucleus extending to the median eminence and throughout the periventricular zone of the hypothalamus. Prodynorphin/proNKB fibers were also identified in the paraventricular nucleus, anterior hypothalamic area, medial preoptic area, median preoptic nucleus, anteroventral periventricular nucleus, and bed nucleus of the stria terminalis in a distribution consistent with previously described arcuate nucleus projections. Interestingly, the majority of prodynorphin-ir neurons in the arcuate nucleus expressed NK3R, and nearly 100% of the prodynorphin-ir neurons contained nuclear ERalpha. Our results suggest that there is a close functional relationship between dynorphin and NKB peptides within the arcuate nucleus of the rat, which may include an autofeedback loop mediated through NK3R. The diverse hypothalamic projections of fibers expressing both prodynorphin and proNKB provide evidence that these neurons may participate in a variety of homeostatic and neuroendocrine processes.
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Coexpression of kisspeptin, NKB and dynorphin has been identified in the arcuate nucleus of the mouse, rat, goat, monkey and sheep.
“Coexpression of kisspeptin, NKB and dynorphin (the KNDy peptides) have been identified in the arcuate nucleus of the mouse, rat, goat, monkey and sheep (Burke et al., 2006; Goodman et al., 2007; Navarro et al., 2009; Ramaswamy et al., 2010; Rance and Bruce, 1994; Rometo et al., 2007; Smith, 2009; Smith et al., 2005a; Wakabayashi et al., 2010).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Burke et al., 2006
Arcuate dynorphin neurons were reduced by 76% after NK3-SAP.
“Arcuate dynorphin neurons were reduced by 76% (Mittelman-Smith et al., 2012b), consistent with the percentage of these neurons that express NK3R (Burke et al., 2006).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Burke et al., 2006
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“A similar dense plexus of NKB/Dyn fibers has been reported in the ARC of the rat and sheep (Burke et al., 2006; Foradori et al., 2006), and an electron microscopic study in the sheep revealed that Dyn neurons in the ARC receive synaptic contact with Dyn fibers (Foradori et al.”
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- Authors
- Burke, M. C., Letts, P. A., Krajewski, S. J., & Rance, N. E.
- Affiliations
- University of Arizona (US)
- Corresponding author
- Rance, Naomi E.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2006-08-17
- Volume
- 498
- Issue
- 5
- Pages
- 712-726
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W1977946309
- Cited by
- 280
- References
- 57
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 22 · 2020: 10 · 2019: 13 · 2018: 23 · 2017: 16 · 2016: 19 · 2015: 19 · 2014: 24 · 2013: 21 · 2012: 24
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG09214, T32AG007434)
- 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
- dynorphin, neurokinin B, prodynorphin, arcuate nucleus, hypothalamus, neurokinin-3 receptor, estrogen receptor alpha, hypothalamic projections, median eminence, paraventricular nucleus, bed nucleus of the stria terminalis, neuroendocrine regulation
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Cell Count, Enkephalins, Female, Immunohistochemistry, Neural Pathways, Neurons, Protein Precursors, Tissue Distribution, Neurokinin B, Rats, Sprague-Dawley, Receptors, Tachykinin, Rats
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