engleski

Effect of sex hormones on renal and hepatic oxalate transporters sat-1 and CFEX in rats

Oxalate is a major constituent in ~80% of all kidney stones. In humans and experimental animals, the incidence of oxalate kidney stones is ~2-fold higher in males then in females. Oxalate can enter circulation either as an end-product of liver metabolism or, being present in various foodstuffs, via absorption in the gastrointestinal tract. If blood oxalate is low, oxalate is mainly excreted via the glomerular filtration. However, if the oxalate concentration in blood is high, or the glomerular filtration is impaired, epithelial cells in the renal proximal tubule and small and large intestine can actively transport and secrete oxalate. This secretion is mediated by the Slc26 family of proteins. The aim of our study was to identify if in rats, gender differences exist in the oxalate-transporting proteins sat-1 (sulfate anion transporter 1 ; Slc26a1) and CFEX (chloride/formate exchanger ; Slc 26a6) in the two major oxalate-handling organs, liver and kidneys. Using various methods (colorimetric measurement of blood and urine oxalate, immunocytochemistry in tissue cryosections, , Western blotting and transport studies in isolated membranes, real time RT-PCR), we have demonstrated that the males are dominant over females regarding: a) oxalate concentration in blood and urine, b) rate of sulfate/oxalate exchange in membrane vesicles isolated from the renal and liver tissues, and c) expression of sat-1 protein in the kidney and liver, and of CFEX protein in the kidney. Furthermore, we have shown that the lower expression of sat-1 protein in females is driven by estrogens inhibition. On the other side, the male-dominant gender differences of CFEX are driven by both estrogen inhibition in females and androgen stimulation in males. However, the expression of sat-1 mRNA did not show gender differences in both liver and kidneys, thus indicating that the observed gender differences on the protein level of sat-1 are posttranscriptional in nature. Our results thus show that higher incidence of oxalate stones in male rats (and possibly in men) may be related to higher urine secretion of oxalate via sat-1 and CFEX transporters, which exhibit the male-dominant expression.

sex differences; oxalate transport; transporters; kidney; liver

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