title: Kinesin superfamily-associated protein 3 is preferentially expressed in glutamatergic neurons and contributes to the excitatory control of female puberty.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea.
authors.forename: Jungil
authors.initials: J
authors.lastname: Choi
authors.forename: Chang Man
authors.initials: CM
authors.lastname: Ha
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Choi
authors.forename: Choon Soo
authors.initials: CS
authors.lastname: Jeong
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Baik
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Maria E
authors.initials: ME
authors.lastname: Costa
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Ojeda
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000502:physiology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020319:Oligodeoxyribonucleotides, Antisense; D050599:Vesicular Glutamate Transport Protein 2; D007987:Gonadotropin-Releasing Hormone; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid