This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Choi, J. Articles by Lee, B. J. Search for Related Content PubMed PubMed Citation Articles by Choi, J. Articles by Lee, B. J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB GLUTAMIC ACID HYDROCHLORIDE

Kinesin Superfamily-Associated Protein 3 Is Preferentially Expressed in Glutamatergic Neurons and Contributes to the Excitatory Control of Female Puberty

Department of Biological Sciences (J.C., C.M.H., E.J.C., C.S.J., J.W.P., B.J.L.), College of Natural Sciences, University of Ulsan, Ulsan 680-749, South Korea; School of Life Sciences and Biotechnology (J.-H.B.), Korea University, Seoul 136-701, South Korea; Department of Neurobiology (J.-Y.P.), Gyeongsang National University College of Medicine, Jinju 660-751, South Korea; and Division of Neuroscience (M.E.C., S.R.O.), Oregon National Primate Research Center/Oregon Health and Science University, Beaverton, Oregon 97006

Address all correspondence and requests for reprints to: Byung Ju Lee, Ph.D., Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea. E-mail: bjlee{at}ulsan.ac.kr; or Sergio R. Ojeda, D.V.M., Division of Neuroscience, Oregon National Primate Research Center/Oregon Health and Science University, Beaverton, Oregon 97006. E-mail: ojedas{at}ohsu.edu.

It was earlier shown that expression of kinesin superfamily-associated protein 3 (KAP3), involved in the neuronal anterograde, microtubule-dependent transport of membrane organelles, increases in the hypothalamus of female rats during the juvenile phase of sexual development. KAP3 mRNA is abundant in the hypothalamus, suggesting that it might be expressed in broadly disseminated neuronal systems controlling neuroendocrine function. The present study identifies one of these systems and provides evidence for an involvement of KAP3 in the excitatory control of female puberty. In situ hybridization and immunohistofluorescence studies revealed that the KAP3 gene is expressed in glutamatergic neurons but not in GABAergic or GnRH neurons. Hypothalamic KAP3 mRNA levels increase during the juvenile period of female prepubertal development, remaining elevated throughout puberty. These changes appear to be, at least in part, estradiol dependent because ovariectomy decreases and estradiol increases KAP3 mRNA abundance. Lowering hypothalamic KAP3 protein levels via intraventricular administration of an antisense oligodeoxynucleotide resulted in reduced release of both glutamate and GnRH from the median eminence and delayed the onset of puberty. The median eminence content of vesicular glutamate transporter 2, a glutamate neuron-selective synaptic protein, and synaptophysin, a synaptic vesicle marker, were also reduced, suggesting that the loss of KAP3 diminishes the anterograde transport of these proteins. Altogether, these results support the view that decreased KAP3 synthesis diminishes GnRH output and delays female sexual development by compromising hypothalamic release of glutamate.