The
sulfate anion transporter (sat-1, Slc26a1) has been cloned from rat liver, functionally characterized, and localized to the sinusoidal membrane in hepatocytes and basolateral membrane (BLM) in proximal tubules (PT). Here, we confirm previously described localization of sat-1
protein in rat liver and kidneys and report on gender differences (GD) in its expression by immunochemical, transport, and excretion studies in rats. The approximately 85-kDa sat-1
protein was localized to the sinusoidal membrane in hepatocytes and BLM in renal cortical PT, with the male-dominant expression. However, the real-time reverse-transcription polymerase chain reaction data indicated no GD at the level of sat-1
mRNA. In agreement with the
protein data, isolated membranes from both organs exhibited the male-dominant exchange of radiolabeled
sulfate for
oxalate, whereas higher
oxalate in plasma and 24-h urine indicated higher
oxalate production and excretion in male rats. Furthermore, the expression of liver, but not renal, sat-1
protein was: unaffected by
castration, upregulated by
ovariectomy, and downregulated by
estrogen or
progesterone treatment in males. Therefore, GD (males > females) in the expression of sat-1
protein in rat liver (and, possibly, kidneys) are caused by the female
sex-hormone-driven inhibition at the posttranscriptional level. The male-dominant abundance of sat-1
protein in liver may conform to elevated uptake of
sulfate and extrusion of
oxalate, causing higher plasma
oxalate in males.
Oxalate is then excreted by the kidneys via the basolateral sat-1 (males > females) and the apical CFEX (Slc26a6; GD unknown) in PT and eliminated in the urine (males > females), where it may contribute to the male-prevailing development of
oxalate urolithiasis.