The effect sex chromosomal complement (SCC) on the expression of sodium transporters is dependent on gonadal sex

Abstract

The sex chromosome complement (SCC) has been demonstrated to have sex‐steroid‐ independent effects on the male versus female phenotype. To examine the role of the SCC in blood pressure (BP), we created a mouse model by translocation of Sry gene, a testes‐determining gene, onto an autosome in both XX and XY mice. Recently, we showed that ovariectomized mice with the XX SCC had higher angiotensin II (Ang II)‐induced BP as compared to the XY SCC. This effect appeared dominant in mice that were gonadally female at birth. The expression of renal sodium transporters may affect BP. To avoid the activational effect of steroidal hormones, mice were either ovariectomized (OVX) or castrated (CAS) depending upon their gondal sex at birth. All mice were infused with Ang II (A, 800 ng/kg•bw/min, n=5/group) for 7 days. Western blotting revealed that OVX‐XY mice had significantly reduced protein abundance for NaKATPase α‐1subunit and γENaC relative to OVX‐XX mice (band density % XX; for NaKATPase were 63 ± 0.01 vs. 100 ± 0.09 %; for γENaC 72.6 ± 0.03 vs. 100 ± 0.09% ). However, no significant difference due to SCC in these protein levels was observed in the CAS XXSry and XY− Sry male (at birth) mice. Moreover, AQP‐3 was significantly reduced in XY− Sry mice relative to XXSry (62.6 ± 0.12 vs. 100 ± 0.07 %). These data demonstrate that the SCC may influence expression of renal sodium and water transporters independently of activational effects of the gonadal steroids. Increased expression of Na‐K‐ATPase or γENaC could play a role in the increased BP observed in the XX SCC mice. The fact that the XX SCC appeared to increase BP suggests that without the overlay of sex steroids, female mice may be have a greater susceptibility to high BP. This may have particular relevance in menopause. NIH