Compensatory mechanisms for GnRH production in Fgf8-deficient mice

Undergraduate Honors Thesis

Citations

Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/nc580n220

Abstract

GnRH (gonadotropin-releasing hormone) is a peptide hormone produced by neurons from the brain and is indispensable for the onset and maintenance of vertebrate reproduction. The development of GnRH neurons relies greatly on fibroblast growth factor (Fgf) signaling. In fact, it has been shown that in fibroblast growth factor 8-deficient (F8 Het) mice, the number of GnRH neurons is reduced by about 50%. Interestingly, F8 Het males and females appear to compensate for this reduction by undergoing normal puberty and producing normal levels of the GnRH peptide before 60 days of age. However, the mechanisms for this compensation are unknown. We hypothesized that F8 Het mice may compensate for a defected GnRH system by increasing the production of transcripts for: (1) GnRH, (2) two GnRH prohormone processing enzymes, CPE and PCSK2, and (3) KiSS1, an upstream stimulator of GnRH release and neuronal activity. Accordingly, the goal of this project was to use quantitative polymerase chain-reaction (qPCR) to investigate if genes involved in these three levels of GnRH system control were upregulated in F8 Het mice. Our results suggest that none of mechanisms proposed were responsible for the plasticity observed. In fact, F8 Het mice harbored significant defects in both GnRH and KiSS1 expression. Our results highlight the complex levels of control that drive the function of the GnRH system and suggest other compensatory mechanisms that we have not yet identified are at play.

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