期刊
JOURNAL OF NEUROSCIENCE
卷 29, 期 38, 页码 11859-11866出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1569-09.2009
关键词
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资金
- Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health (NICHD/NIH) [U54 HD12629, R01 HD27142]
- University of Washington Center for Research in Reproduction and Contraception
- National Institute on Drug Abuse/NIH [R01 DA016898, K05 DA020570]
- Fulbright/MEC Program of the United States Department of State and Ministerio Espanol de Ciencia e Innovacion
- Marie Curie Outgoing International Fellowship supported by the 7th Frame Programme of the European Union
- Program for Promotion of Basic Research Activities for Innovative Bioscience (PROBRAIN) of Japan
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 Dynand NKB inhibit LH secretion. Moreover, using Dynand 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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