Effect of sex chromosome complement versus gonadal hormones on abundance of renal transporters.

Sex differences in renal tubular salt and water transporters, channels, claudins and regulatory factors are evident all along the nephron. The influence of sex hormones on physiologic dimorphisms has been established in studies removing, inhibiting or restoring sex hormones and their receptors. The influence of the sex chromosome complement (SCC, XY vs. XX) on renal transporter abundance and activity is an open question. We employed the Four Core Genotypes (FCG) mouse model (in which the testis determining SRY gene is deleted from the Y chromosome and inserted onto an autosomal chromosome) to compare abundance of more than fifty renal transporters and regulators in: FXX gonadal females, FXY gonadal females, MXX Sry males, and MXY XYSry males using semi-quantitative immunoblots. In addition to establishing the significant influence of gonadal hormones, we show, for the first time, that SCC contributes to sexual dimorphisms in abundance of renal transporters including: NHE3, SGLT1 and 2, AQP1, mNKAα1 and β1, NCC, and ENaC β and γ subunits. The findings in this FCG model analysis provide the foundation for future studies of the role of sex hormones vs. chromosomes on physiologic parameters including filtration and flow, on transporter covalent modifications, and trafficking in both heath and disease.