Distribution and sex differences in expression of P-GLYCOPROTEIN (P-gp/Mdr1/Abcb1) in rat liver, kidneys, and gastrointestinal tract

P-gp is an ATP-dependent transmembrane efflux transporter constitutively expressed in the membrane of hepatocyte bile canaliculi (BC), brush border membrane (BBM) of the renal proximal tubule (PT) and intestinal epithelium, blood-tissue barriers, maternal-fetal barriers, and hematopoietic cells. Sex steroids regulate P-gp expression and function in the rat liver, exhibiting female (F) dominant sex differences. However, the hormone(s) responsible for these differences in the rat liver, and possibly in other P-gp expressing organs, have not been resolved. Here we used the commercial monoclonal antibody (clone C219) to study effects of sex and gonadectomy on the localization and abundance of P-gp by immunocytochemistry (IC) and Western blotting (WB) in the liver, kidneys, and gastrointestinal tract of adult male (M) and F Wistar rats. We confirmed sex differences (M < F) in the P-gp expression in BC, and found that gonadectomy in M increases this expression. In the kidneys, the antibody stained BBM of the PT S2 segments in the M cortex (CTX) and S3 segments in medullary rays and outer stripe (OS) in both M and F. Gonadectomy in M, but not in F, increased the P-gp expression in OS and decreased in CTX. In the small intestine, the P-gp abundance increased from proximal to distal segments, but possible sex differences or effects of gonadectomy could not be detected due to high variability of the P-gp expression. The data indicate that in rats, androgens inhibit the expression of P-gp in BC and PT S3 segmenst, and stimulate it in the PT S2 segments.