Effect of ovariectomy on renal estrogen receptor-α and estrogen receptor-β in young salt-sensitive and -resistant rats

This study evaluated the effect of ovariectomy on renal estrogen receptor (ER)-alpha and ER beta expression in young female Dahl salt-sensitive and salt-resistant rats. Our hypothesis was that estrogen depletion results in an imbalance in ER alpha and ER beta expression in salt-sensitive rats. Rats were subjected to sham surgery (intact), ovariectomy, and ovariectomy with estrogen replacement. Kidneys were harvested 8 weeks later. Western blot was used to measure ER alpha and ER beta expression in the cortex and medulla. In intact rats, ER alpha was 2.7- and 4.3-fold higher in salt-sensitive compared with salt-resistant rats in the renal cortex and medulla, respectively. In salt-sensitive rats, ovariectomy caused 42% and 52% decreases in ER alpha and 107% and 314% increases in ER beta in renal cortex and medulla, respectively. In salt-resistant rats, ovariectomy caused 33% and 150% increases in ER alpha and 107% and 100% increases in ER beta in renal cortex and medulla, respectively. Estrogen replacement did not alter ER alpha but restored ER beta expression levels similar to levels in intact rats in both salt-sensitive and salt-resistant rats. Thus, estrogen loss had opposite effects on ER alpha in salt-sensitive (downregulation) and salt-resistant rats (upregulation). We propose that the decrease in ER alpha expression in salt-sensitive rats after estrogen loss alters the balance of renal ERs and may play a role in accelerating the development of hypertension and renal damage.