Session: OR04-GnRH & Gonadotroph Biology & Signaling
Room 135 (Moscone Center)
Aim: To define further GnRH neuronal signaling by kiss-Gpr54 and resulting physiological outcomes.
Methods and results: A GnRH neuron-specific Gpr54 knockout (GnRH-Gpr54KO) mouse model was generated and reproductive development and fertility was assessed. Exon 2 of Gpr54 was surrounded by LoxP sites in a targeting construct that also included a Frt flanked neomycinr selection cassette. The targeting construct was electroporated into ES cells, and six positive targeted clones were obtained. The Gpr54 “floxed” animals were crossed to GnRH-Cre mice. Cre recombinase expression in GnRH neurons produced a cell-specific Gpr54 KO. A delay in pubertal onset in females was observed. The mean day of vaginal opening in wild-type littermates was 27 (±0.20) days versus 39 (±1.4) days in GnRH-Gpr54KO mice (n=5, P≤0.001). The first day in estrus and estrous cycles were monitored by vaginal lavages. Absence of the first day in estrus and estrous cyclicity were observed in the GnRH-Gpr54KO female mice. In addition, infertility was observed in both female and male GnRH-Gpr54KO mice.
Conclusion: Taken together, these data provide in vivo evidence that Gpr54 in GnRH neurons is critical for reproductive development and fertility. This work provides new insight into the physiological role of Gpr54 in mediating GnRH neuronal function and mammalian reproduction.
Disclosure: SR: Ad Hoc Consultant, CVS/Caremark, Speaker, Novo Nordisk. Nothing to Disclose: HJN, GEH, YK, AMW
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