The wild ground squirrel is a typical seasonal breeder. In this study, using RT-PCR, western blot and immunohistochemistry, we investigated the mRNA and protein expressions of androgen receptor (AR), estrogen receptors Î± and Î² (ERÎ± and ERÎ²) and aromatase cytochrome P450 (P450arom) in the medial preoptic area (MPOA) of hypothalamus of the wild male ground squirrel during the breeding season (April), the non-breeding season (June) and pre-hibernation (September). AR, ERÎ±, ERÎ² and P450arom protein/mRNA were present in the MPOA of all seasons detected. The immunostaining of AR and ERÎ± showed no significant changes in different periods, whereas ERÎ² and P450arom had higher immunoreactivities during the breeding season and pre-hibernation when compared to those of the non-breeding season. Consistently, both the protein and mRNA levels of P450arom and ERÎ² were higher in the MPOA of pre-hibernation and the breeding season than in the non-breeding season, whereas no significant difference amongst the three periods was observed for AR and ERÎ± levels. These findings suggested that the MPOA of hypothalamus may be a direct target of androgen and estrogen. Androgen may play important regulatory roles through its receptor and/or the aromatized estrogen in the MPOA of hypothalamus of the wild male ground squirrels.