Naslov
Rat renal OAT1 exhibits gender differences that are determined by both androgen stimulation and estrogen inhibition

Autori
Sabolić, Ivan ; Ljubojević, Marija ; Herak-Kramberger, Carol-Mirna ; Hagos, Yohannes ; Bahn, Andrew ; Endou, Hitoshi ; Burckhardt, Gerhard

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

Izvornik
PharmaConference 2003 - Transporters & Drugs / Hediger, Matthias A ; Meier-Abt, Peter ; Burrier, Robert ; Endou, Hitoshi - Pontresina : Organizacijski odbor, 2003

Skup
3rd International Research Conference PharmaConference 2003: Transporters & Drugs

Mjesto i datum
Pontresina, Švicarska, 17.08.2003. - 21.08.2003

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Organic anion transporters; sex differences; steroid hormones

Sažetak
The organic anion transporter OAT1, a member of the OAT family that plays a major role in secretion of p-aminohippurate (PAH) and a variety of other organic anions, has been immunolocalized in human and rat kidneys to the basolateral membrane (BLM) of the proximal tubule S2 segment. In rats, the secretion of PAH and the expression of OAT1 protein was found to be stronger in males (M) than in females (F), but hormones responsible for these gender differences have not been defined. By using immunofluorescence cytochemistry in cryosections of fixed kidney tissue and immunoblotting of isolated renal cortical BLM and total cell membranes, we studied localization and abundance of OAT1 in adult and prepubertal M and F rats, as well as effects of gonadectomy and steroid hormone replacement therapy in gonadectomized adult animals. The principal basolateral immunolocalization of OAT1 in the S2 segment, and sex differences in its expression in adult rats (M>F) were confirmed by both methods. The cells in the proximal tubule S3 segments also exhibited a limited expression of OAT1 both in the BLM and intracellularly. Two weeks following castration of adult M, the abundance of OAT1 in total cell membranes decreased by 45%, whereas daily treatment of castrated M for 8 days with testosterone, estradiol, or progesterone (each 2.5 mg/kg b.m., s.c.) resulted in a complete restitution, further depression (by 88%), or overexpression (by 22%) of the protein, respectively. In adult F rats, ovariectomy had no effect, but the treatment of ovariectomized F with estradiol caused a decrease by 73% of OAT1 abundance in total cell membranes. The observations by immunocytochemistry in tissue cryosections from sham-operated, gonadectomized and hormone-treated gonadectomized rats completely matched the findings in immunoblotting experiments. Furthermore, in prepubertal (4 week-old) rats, the abundance of OAT1 protein in total cell membranes, and the intensity of immunofluorescence staining in tissue cryosections were low, and exhibited no sex differences. These data indicate that gender differences in renal OAT1 (M>F) appear after puberty and are determined by both a stimulatory effect of androgens and progesterone, and an inhibitory effect of estrogens.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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