Naslov
Renal expression of organic anion transporter OAT5 in rats is regulated by sex hormones

Autori
Sabolić, Ivan ; Breljak, Davorka ; Ljubojević, Marija ; Balen, Daniela ; Žlender, Vilim ; Brzica, Hrvoje ; Kušan, Marija ; Anzai, Naohiko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
BioMedical Transporters 2007 : Membrane Transporters in Disease and Drug Development / Hediger, Matthias A. - Bern : University of Bern, 2007, 72-72

Skup
5th International Research Conference : BioMedical Transporters 2007 : Membrane Transporters in Disease and Drug Development

Mjesto i datum
Bern, Švicarska, 12.08.2008. - 16.08.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
gender differences; sex differences; kidney; androgens; estrogens; progesterone

Sažetak
Organic anion transporter 5 (Oat5, Slc22a19) is a kidney-specific drug transporter that has been cloned, characterized as an organic anion/ dicarboxylate exchanger, and localized to the brush border (BB) of proximal tubule (PT) straight segment (S3) in the rat and mouse kidney, with similar levels of mRNA expression in female (F) and male (M) animals. Here we report on sex hormone-regulated expression of the rat kidney Oat5 (rOat5) after reinvestigating: a) expression of its mRNA by end-point and real time PCR in various tissue zones, b) abundance of its protein by Western blotting (WB) in isolated membranes from various tissue zones, and c) 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, a polyclonal rOAT5-antibody labeled in non-reducing conditions a single protein band of ~72 kDa that 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), exhibiting zonal differences (OS>cortex). In both tissue zones, the immunostaining was much stronger in F, proving gender differences (F>M), 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 higher than in adult M and lower than in adult F, but gender-independent. Conclusion: in rats, the renal Oat5 is localized to the BB of PT (S3>S2), and exhibits zonal (OS>cortex) and gender differences (F>M) that appear after puberty due to strong androgen inhibition and weak estrogen and progesterone stimulation.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA