The liver and kidney expression of sulfate anion transporter sat-1 in rats exhibits male-dominant gender differences.
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.
Brzica
Hrvoje
H
Unit of Molecular Toxicology, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10001 Zagreb, Croatia.
Breljak
Davorka
D
Krick
Wolfgang
W
Lovrić
Mila
M
Burckhardt
Gerhard
G
Burckhardt
Birgitta C
BC
Sabolić
Ivan
I
D000818:Animals; D027321:Anion Transport Proteins / Q000096:biosynthesis*; D017920:Antiporters / Q000096:biosynthesis*; D002369:Castration; D002462:Cell Membrane / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010070:Oxalates / Q000652:urine; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D000076988:Sulfate Transporters; D013431:Sulfates / Q000378:metabolism
D027321:Anion Transport Proteins; D017920:Antiporters; D010070:Oxalates; D012333:RNA, Messenger; C056459:Slc26a1 protein, rat; D000076988:Sulfate Transporters; D013431:Sulfates; D011374:Progesterone; D004958:Estradiol; C023482:estradiol dipropionate