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The Journal of Neuroscience, June 21, 2006, 26(25):6687-6694; doi:10.1523/JNEUROSCI.1618-06.2006
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Behavioral/Systems/Cognitive
Kiss1 Neurons in the Forebrain as Central Processors for Generating the Preovulatory Luteinizing Hormone Surge
Jeremy T. Smith,1 Simina M. Popa,3 Donald K. Clifton,2 Gloria E. Hoffman,4 andRobert A. Steiner1,2 Departments of 1Physiology and Biophysics and 2Obstetrics and Gynecology and 3Undergraduate Program in Neurobiology, University of Washington, Seattle, Washington 98195, and 4Department of Anatomy and Neurobiology, University of Maryland, School of Medicine, Baltimore, Maryland 21201
Correspondence should be addressed to Robert A. Steiner, Department of Physiology and Biophysics, Health Sciences Building, G-424, School of Medicine, University of Washington, Box 357290, Seattle, WA 98195-7290. Email: steiner{at}u.washington.edu
Kisspeptins are neuropeptides encoded by the Kiss1 gene, which have been implicated in the neuroendocrine regulation of gonadotropin-releasing hormone (GnRH) secretion. The goal of this study was to test the hypothesis that activation of Kiss1 neurons in the anteroventral periventricular nucleus (AVPV) is linked to the induction of the preovulatory luteinizing hormone (LH) surge in the rat. First, we determined that levels of Kiss1 mRNA in the AVPV peaked during the evening of proestrus, whereas Kiss1 mRNA in the arcuate nucleus (Arc) was at its nadir. Second, we corroborated this observation by demonstrating that Kiss1 mRNA is increased in the AVPV at the time of an estrogen (E)- and progesterone-induced LH surge in ovariectomized animals, whereas in the Arc, the expression of Kiss1 mRNA was decreased. Third, we found that most Kiss1 neurons in the AVPV coexpress the immediate early gene Fos coincidently with the LH surge, but virtually none coexpressed Fos on diestrus. In contrast, Kiss1 neurons in the Arc were Fos negative at the time of the LH surge as well as on diestrus. Finally, we found that most Kiss1 neurons in the AVPV and Arc express estrogen receptor
mRNA, suggesting that E acts directly on these neurons. These results suggest that Kiss1 neurons in the AVPV play an active role in mediating the effects of E on the generation of the preovulatory GnRH/LH surge on proestrus.
Key words: Kiss1 mRNA; kisspeptin; metastin; AVPV; arcuate; estrogen; progesterone
Received April 14, 2006; revised May 10, 2006; accepted May 10, 2006.
Correspondence should be addressed to Robert A. Steiner, Department of Physiology and Biophysics, Health Sciences Building, G-424, School of Medicine, University of Washington, Box 357290, Seattle, WA 98195-7290. Email: steiner{at}u.washington.edu
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