Undergraduate Honors Thesis


The Effect of Androgen Injections on Male FGF8 Hypomorphic Mice Public Deposited

  • Gonadotropin-releasing hormone (GnRH) neurons are responsible for the development and regulation of reproductive function in all vertebrates. The disruption of the GnRH system can lead to severe reproductive impairment and infertility in both human and mice. Interestingly, a fraction of these reproductive impairment cases can be reversed with the chronic treatment of androgens, suggesting androgens may upregulate genes neurotrophic to GnRH neurons. The objective of this study was to use a candidate gene approach to examine if the expression of four genes previously found to be neurotrophic to GnRH neurons was altered by androgen treatment. These genes included a prototypic fibroblast growth factor ligand (FGF2), two FGF receptors (FGFR1 and FGFR3), and brain-derived neurotrophic factor (BDNF). Male wildtype (WT) and heterozygous FGF8 hypomorphic (FGF8 Het) mice were used. The latter harbored FGF8 deficiency which resulted in ~50% reduction in GnRH neurons. WT and FGF8 Het mice were injected subcutaneously with 500 μg testosterone enanthate (TE) every week from postnatal day (PN) 60-88 and sacrificed on PN95. Somatic, testicular, and seminal vesicle (SV) mass was measured, and the expression of four candidate genes was quantified in the preoptic area (POA) by quantitative PCR (qPCR). TE treatment significantly increased the growth trajectory of FGF8 Het mice, suppressed testicular mass, and enhanced SV mass. Surprisingly, TE significantly downregulated FGF2 expression but did not alter the expression of the remaining three genes. Several explanations could account for these observations, including the potential role of aromatization, the possible involvement of translational regulation, and the heterogeneity of cell populations in the POA. Together, these results suggested either the involvement of additional genes or neurotrophic mechanisms that may underlie the benefits of androgen treatment on the GnRH system. Supported by NIH R01 HD083260 to PST.

Date Awarded
  • 2022-10-28
Academic Affiliation
Committee Member
Granting Institution
Last Modified
  • 2022-11-09
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