SAT-408 Inducible Kiss1 Knockout in the Hypothalamic Arcuate Nucleus Suppressed Pulsatile LH Secretion in Male Mice

Accumulating evidence suggests that kisspeptin/Gpr54 signaling is indispensable for GnRH/gonadotropin secretion and consequent reproductive functions in mammals. Conventional Kiss1 knockout mice and rats are reported to be infertile. To date, however, no report investigating the effect of inducible central Kiss1 knockout on pulsatile gonadotropin release is available. Here we report in vivo analysis of inducible conditional Kiss1 knockout male mice generated by infection with adeno-associated virus (AAV) vectors driving Cre recombinase (AAV-Cre) in the brain of Kiss1-floxed male mice, in which exon 3 of the Kiss1gene were floxed with LoxP sites. Adult Kiss1-floxed male mice were injected with AAV-Cre or AAV vectors driving GFP (AAV-GFP) bilaterally into the hypothalamic arcuate nucleus (ARC). Four weeks after the AAV-Cre injection, the male mice showed profound decrease in the number of ARC Kiss1-expressing cells and luteinizing hormone (LH) pulse frequency. Interestingly, pulsatile LH secretion was apparent 8 weeks after the AAV-Cre injection despite the suppression of ARC Kiss1 expression. The control Kiss1-floxed animals infected with AAV-GFP showed apparent LH pulses and Kiss1 expression in the ARC both at 4 or 8 weeks after the AAV-GFP injection. These results suggest that ARC Kiss1-expressing cells are responsible for pulsatile LH secretion in male mice and the possibility of compensation mechanism to restore GnRH/LH pulse generation in central Kiss1 knockout mice. This work was supported in part by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research 18H03973 (to H.T.).