Sex differences in <scp>PRA</scp> and <scp>PRB</scp> expression in the neonatal mouse brain

During development, there is a significant sex difference in the expression of progestin receptor (PR) in the medial preoptic nucleus (MPN) of rodents. Males express high levels of PR immunoreactivity (PR-ir) in the MPN beginning at embryonic day 19, whereas PR is virtually absent in females until the second postnatal week. This sex difference indicates a developmental window during which the male MPN is more sensitive to progestins than the female MPN. The two PR isoforms, full-length PRB and the truncated PRA, can differentially regulate the expression of specific genes. Yet, it is unknown how these isoforms contribute to the sex difference in PR expression. In the present study, we investigated the relative contributions of PRA and PRB expression in the MPN during development. PR-ir in neonatal male and female PRA knockout (PRAKO) or PRBKO mice were compared with their wildtype (WT) counterparts. In the MPN, levels of PR-ir were higher in WT males than in WT females consistent with previous results from our lab. Moreover, this sex difference was also detected in both PRAKO and PRBKO mice, suggesting that both isoforms contribute to PR expression in males. We also investigated the expression of PRA and PRB in the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMN) and arcuate nucleus (ARC), two additional brain regions implicated in progestin function in reproduction in which males expressed PR at higher levels than females. Interestingly, in the VMN and the ARC, PRA was the predominant isoform. These findings suggest that the differential expressions of PRA and PRB result in sex differences in PR in the brain regions associated with sexually dimorphic behaviors and neuroendocrine functions.