engleski

The Expression of Organic Anion Transporter Oat5 in Rat Kidney Is Gender-Dependent

The organic anion transporter 5 (Oat5, Slc22a19) has been cloned, characterized as a kidney-specific organic anion/dicarboxylate exchanger, and localized to the brush border (BB) of proximal tubule (PT) straight segment (S3) in the rat and mouse kidney. Similar levels of Oat5 mRNA expression in the kidney of female (F) and male (M) mice suggested an absence of gender differences. Here we report that the expression of renal Oat5 (rOat5) in rats is regulated by sex-hormones after studying: a) the expression of its mRNA by end-point and real time PCR in various tissue zones, b) the abundance of its protein by Western blotting (WB) in isolated membranes from various tissue zones, and c) the localization of its protein by immunocytochemistry (IC) in tissue cryosections. In adult rats, the expression of rOat5 mRNA was predominant in the outer stripe (OS) ; in intact animals, it exhibited strong gender differences (F>M), upregulation by castration and downregulation by ovariectomy, whereas in castrated M, it was strongly downregulated by testosterone and weakly upregulated by estradiol and progesterone treatment. By WB, an rOAT5-antibody labeled a single protein band of ~72 kDa, which in variously-treated animals exhibited a density pattern comparable to that of mRNA. By IC in intact rats, the rOat5 protein was localized to the BB of convoluted PT in the cortex (weakly) and S3 in the OS and medullary rays (strongly). In both tissue zones, the immunostaining was stronger in F, whereas the intensity pattern in gonadectomized M and F, and in sex hormone-treated castrated M, matched the pattern of mRNA and WB data. In prepubertal rats, the expression of rOat5 mRNA and its protein was similar to that in adult M, and gender-independent. Conclusion: in rat kidneys, Oat5 is localized to the BB of PTs (S1~S2<S3), where it exhibits zonal (cortex<OS) and gender differences (F>M) which appear after puberty due to strong androgen inhibition and weak estrogen and progesterone stimulation.

gender differences; sex differences; proximal tubule; rodents; organic anions

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