Naslov
Expression of organic anion transporter Oat3 in rat liver is regulated by sex hormones

Autori
Breljak, Davorka ; Ljubojević, Marija ; Balen, Daniela ; Žlender, Vilim ; Anzai, Naohiko ; Burckhardt, Gerhard ; Sabolić, Ivan

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, 49-49

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

Mjesto i datum
Bern, Švicarska, 12.08.2007. - 16.08.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
gender differences; sex differences; membrane transporters; organic anions; androgens; estrogens; progesterone

Sažetak
In the mammalian liver, endogenous and exogenous organic anions are eliminated by several organic anion transporters (OAT) that belong to the Slc22 family of solute carriers. The rat liver OAT3 (rOat3, Slc22a8) has been cloned, characterized as a dicarboxylate exchanger, and found to be male-predominant due to much stronger expression of its mRNA in male (M) than in female (F) animals. However, the expression of rOat3 protein and its cellular localization in rat hepatocytes are unknown. In order to describe in more detail the expression of rOat3 at mRNA and protein levels in the rat liver, we investigated: a) expression of rOat3 mRNA by end-point RT-PCR and real-time RT-PCR in the tissue, b) abundance of rOat3 protein by Western blotting (WB) in total cell membranes (TCM) isolated from tissue homogenates, and c) cellular localization of rOat3 protein by immunocytochemistry (IC) in tissue cryosections. The experiments were performed in intact adult and prepubertal M and F, castrated M treated with oil (O ; control), testosterone (T), estradiol (E), or progesterone (P), and in intact adult M treated with O, E or P. In intact animals, the data of end-point PCR and real-time RT-PCR confirmed the male-predominant expression of rOat3 mRNA in the rat liver. Castration caused a marked decrease, whereas the treatment of castrates with T restored the expression of rOat3 mRNA to the level of intact M, while the treatment with E and P had no effect in comparison with the O-treated controls. However, the treatment of intact adult M with E and P strongly suppressed the liver rOat3 mRNA expression. In the liver of prepubertal rats, the expression of rOat3 mRNA was weak and similar in both genders. In WB experiments in adult M, a polyclonal anti-rOat3 antibody in non-reducing conditions labeled a single, peptide-blockable protein band of ~50 kDa, which in various experimental conditions exhibited a density pattern comparable to that of rOat3 mRNA. However, the related protein band was absent in TCM from the liver of adult F and prepubertal M and F rats. In IC studies, the antibody strongly stained intracellular organelles of unknown origin only in the liver of intact adult M rats. Our results indicate that rOat3 in the rat liver exhibits: a) strong gender differences (M>F) at both mRNA and protein levels, which appear after puberty due to testosterone stimulation and estradiol and progesterone inhibition, and b) localization in yet to be defined intracellular organelles.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA