17-β estradiol attenuates streptozotocin-induced diabetes and regulates the expression of renal sodium transporters

Diabetes mellitus is associated with natriuresis, whereas estrogen has been shown to be renoprotective in diabetic nephropathy and may independently regulate renal sodium reabsorption. The aim of this study was to determine the effects of 17-beta estradiol (E-2) replacement to diabetic, ovariectomized (OVX) female rats on the expression of major renal sodium transporters. Female, Sprague-Dawley rats (210 g) were randomized into four groups: (1) OVX; (2) OVX+E-2; (3) diabetic+ovariectomized (D+OVX); and (4) diabetic+ovariectomized+estrogen (D+OVX+E-2). Diabetes was induced by a single intraperitoneal injection of streptozotocin (55mg/kg. body weight (bw)). Rats received phytoestrogen-free diet and water ad libitum for 12 weeks. E2 attenuated hyperglycemia, hyperalbuminuria, and hyperaldosteronism in D rats, as well as the diabetes-induced changes in renal protein abundances for the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), and the alpha- and beta-subunits of the epithelial sodium channel ( ENaC), that is, E2 decreased NKCC2, but increased a- and beta-ENaC abundances. In nondiabetic rats, E-2 decreased plasma K+ and increased urine K+/ Na+ ratio, as well as decreased the abundance of NKCC2, beta-ENaC, and alpha-1-Na-K-adenosine triphosphate (ATP)ase in the outer medulla. Finally, the diabetic, E2 rats had measurably lower final circulating levels of E2 than the nondiabetic E2 rats, despite an identical replacement protocol, suggesting a shorter biological half-life of E-2 with diabetes. Therefore, E-2 attenuated diabetes and preserved renal sodium handling and related transporter expression levels. In addition, E-2 had diabetes-independent effects on renal electrolyte handling and associated proteins.