The Journal of neuroscience : the official journal of the Society for NeuroscienceSep 25, 2009

Control of reproductive hormone release by specific brain neurons in mice

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Updated Apr 2, 2026

Abstract

Kiss1 neurons in the arcuate nucleus of female mice express the Dyn and NKB genes along with their respective receptors.

Kiss1 neurons coexpress preprodynorphin and neurokinin B, as well as their receptors.
Expression of Dyn, NKB, and their receptors in Kiss1 neurons is inhibited by estradiol.
Dyn and NKB are associated with the inhibition of luteinizing hormone secretion.
Long-term disruption of Dyn/KOR signaling may compromise the increase in luteinizing hormone after ovariectomy.
A proposed model suggests that NKB and dynorphin may help regulate the secretion of kisspeptin and drive GnRH release.

Simplified

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 kappa 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.

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Control of reproductive hormone release by specific brain neurons in mice

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