Gonadotropin-Releasing Hormone (GnRH), the master regulator of the reproductive axis, is hypothesized to play an essential role in directly sensing changes in energy levels to maintain fertility. There are a number of GnRH cell lines that have been utilized to study reproductive function; however these have been embryonic in origin and clonally derived. To investigate the cellular mechanisms underlying glucose responsiveness in GnRH neurons, we generated a novel GnRH cell line through immortalization, and fluorescent activated cell (FAC)-sorting of hypothalamic primary culture taken from a GnRH-GFP transgenic mouse. The mHypoA-GnRH/GFP neurons express a complement of markers of fully differentiated GnRH neurons. Glucose induces neuronal activation of mHypoA-GnRH/GFP neurons and glucose metabolism initiates an AMP-Protein Kinase (AMPK)-dependent mechanism to exert transcriptional and secretory control of GnRH. These findings support the use of this novel GnRH cell model for defining components involved in cellular and molecular action of glucose in GnRH neurons.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33447 |
| Date | 22 November 2012 |
| Creators | McFadden, Sean Allan |
| Contributors | Belsham, Denise |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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