Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse
By V. Navarro, M. L. Gottsch, C. Chavkin, H. Okamura, D. Clifton, R. Steiner. Journal of Neuroscience, 2009
705 citations recorded by the source corpus.
Kisspeptin is encoded by the Kiss1 gene, and kisspeptin signaling plays a critical role in reproduction. In rodents, kisspeptin neurons in the arcuate nucleus (Arc) provide tonic drive to gonadotropin-releasing hormone (GnRH) neurons, which in turn supports basal luteinizing hormone (LH) secretion. Our objectives were to determine whether preprodynorphin (Dyn) and neurokinin B (NKB) are coexpressed in Kiss1 neurons in the mouse and to evaluate its physiological significance. Using in situ hybridization, we found that Kiss1 neurons in the Arc of female mice not only express the Dyn and NKB genes but also the NKB receptor gene (NK3) and the Dyn receptor [the κ opioid receptor (KOR)] gene. We also found that expression of the Dyn, NKB, KOR, and NK3 in the Arc are inhibited by estradiol, as has been established for Kiss1, and confirmed that Dyn and NKB inhibit LH secretion. Moreover, using Dyn and KOR knock-out mice, we found that long-term disruption of Dyn/KOR signaling compromises the rise of LH after ovariectomy. We propose a model whereby NKB and dynorphin act autosynaptically on kisspeptin neurons in the Arc to synchronize and shape the pulsatile secretion of kisspeptin and drive the release of GnRH from fibers in the median eminence.
Subfields: Molecular Biology, Reproductive Medicine
View Paper: https://www.semanticscholar.org/paper/fc30ffc9a1c1fc2bf018368ed20628ffc92f5bb8
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Citations in the corpus
- Kisspeptins and reproduction: physiological roles and regulatory mechanisms. (2012, methodology): “Thereafter, the presence of such KNDy neurons has been documented by a combination of in situ hybridization and IHC techniques in the mouse, goat, and monkey, although in the latter only NKB coexpression was analyzed (304, 305, 363, 491).”
- Neuropeptide transmission in brain circuits (2012, background): “Dynorphin and neurokinin B colocalize with kisspeptin in many mammals (Goodman et al, 2007); dynorphin is proposed to act back on the releasing kisspeptin neurons to synchronize and shape pulsatile release patterns of kisspeptin (Navarro et al, 2009; Wakabayashi et al, 2010).”