Sex differences in N-linked glycosylation have recently been revealed in total serum proteins in humans in that males have higher levels of many types of N-glycans (Knezevic et al., 2009; Stanta et al., 2010). To date, we have examined N-linked glycosylation of the MOPR only in the thalamus and CPu, which show no sex differences. To the best of our knowledge, N-glycan composition has not been studied in any 7-transmembrane receptor. Another factor that may influence sex-specific MOPR protein expression is the hormonal state of females. Female rats had significantly less MOPR immunoreactivity in the caudal ventrolateral PAG than males, with the greatest difference observed during proestrus (Loyd et al., 2008). However, it remains to be studied whether A112- and G112-MOPRs are differentially modulated by sex-related factors. Epigenetic regulation may also play a role in sex differences. MOPR gene expression is epigenetically programmed in the brain, and methyl-CpG-binding protein 2 (MeCP2) regulates the epigenetic program during DNA methylation and chromatin remodeling of the MOPR promoter (Hwang et al., 2009). Neonatal females express significantly higher levels of MeCP2 than males in
