Water Conservation in Chronic Ethanol Exposure is Associated With Elevated Renal Estrogen Receptor Beta and Vasopressin V2 Receptor mRNA in the Female Rat

Abstract

We previously demonstrated that chronic high dose ethanol intake decreases water load excretion in female but not male rats. We thus hypothesized that sex differences in alteration of water load excretion in response to ethanol is due to changes in renal vasopressin V2 receptor (V2R) expression. Other research has identified estrogen receptor (ER) α and β in renal tissue which may affect renal fluid handling. Thus, in this study we compared renal papilla mRNA expression of V2R, ERα and ERβ between male control (n=5) and ethanol‐fed (n=15) rats, and female control (n=12) and ethanol‐fed (n=17) rats. RT‐PCR analysis revealed that the decreased water excretion observed in ethanol‐exposed females was accompanied by a 40% increase in V2R mRNA (p<0.05) and a 146% increase in ERβ mRNA (p<0.05) compared to controls. In contrast, ethanol treatment in male rats resulted in no difference in water excretion, and yielded no change to V2R or ERβ mRNA expression in the renal papilla. ERα expression was not different between males or females, nor affected by ethanol treatment. Overall, these results suggest that females can better compensate for the dehydrating effects of ethanol exposure by increasing renal responsiveness to vasopressin via upregulating renal V2R. Also, ethanol specifically upregulates the ERβ subtype in the female kidney which may modulate renal sensitivity to vasopressin. Supported by US Army Medical Command.