Objective:To investigate the effects of AQP4 on the interplay between sex hormone and neurotransmitter. Methods: Firstly, we compared the concentrations of estrogen and progestogen between AQP4 knockout and wild type female mice. And then we determined the alterations of monoamine neurotransmitters in ovariectomied female mice. Results:AQP4 knockout decreased the concentrations of estrogen and progestogen. Ovariectomy only induced the decrease of DA in striatum of AQP4+/+ mice, did not alter the levels of DA in AQP4-/- mice. Conclusion:These findings reveal for the first time that AQP4 altered the action of ovarian hormones on monoamine neurotransmitters.