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