MOLECULAR AND STRUCTURAL BASES OF HYPOTHALAMIC PUBERTY

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a subcontract from a project directed by Dr. T. Plant (University of Pittsburgh, PA). The project is aimed at understanding the physiological mechanisms responsible for the onset of puberty in humans. Studies performed in Dr. Ojeda's lab are those proposed under Specific Aim 3 of the main application. Aim 3: To determine, in the absence of interfering testicular hormone feedback, the global profile of hypothalamic gene expression at the time of 1) the suppression of pulsatile GnRH release during infancy, and 2) the resurgence in pulsatile GnRH release at the end of the juvenile phase of development. The rhesus monkey will be used as an experimental paradigm. Standard physiological models will be used to examine whether increased GPR54 signaling will sustain precocious GnRH release. Structural remodeling will be prevented by intrahypothalamic injection of endoneurominidase, and candidate and global gene expression will be examined by RNAse protection and hybridization to gene arrays containing 8,400 human cDNAs (or 8,000-10,000 monkey cDNAs), respectively.