Sex differences in the location of immunochemically defined cell populations in the mouse preoptic area/anterior hypothalamus

The preoptic area/anterior hypothalamus (POA/AH) is sexually dimorphic in many vertebrates. We have defined specific cell populations within the POA/AH using immunocytochemical markers for estrogen receptor β (ERβ) and the R1 subunit of the GABAB receptor (GABABR1). Our previous finding of sex differences in cell migration in this region in embryonic day 15 mice led us to examine sex differences in the location or size of chemically identified cell groups. At embryonic day 17 (E17), cells containing immunoreactive (ir) ERβ in females were located more dorsal and lateral than those in males. In contrast to this positional sex difference seen at E17, ERβ expression at P0 and adulthood showed a sex difference in cell number and area of immunoreactivity with a higher expression of ERβ in males than females. Furthermore, in animals that were genetically deprived of gonadal and adrenal hormones by virtue of a disrupted gene coding for steroidogenic factor 1, cells containing ir ERβ followed a female phenotype for location at E17 and a female phenotype for number of ir cells at P0 regardless of genetic sex, suggesting that circulating hormones may be influencing cell position in the POA/AH. A second phenotypically identified cell group containing ir GABABR1 also had a sex difference in cell positions at E17. Females expressed GABABR1 in cells with a more dorsal position than in males. These results provide support for the suggestion that sex differences in cellular organization in the developing hypothalamus arise from sex differences in cell migration.