Naslov
The expression of SGLT1 along rat proximal tubule exhibits androgen-dependent zonal and gender differences

Autori
Sabolić, Ivan ; Škarica, Mario ; Gorboulev, Valentin ; Ljubojević, Marija ; Balen, Daniela ; Herak-Kramberger, Carol M ; Koepsell, Hermann

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

Izvornik
Gottinger Transporttage 2005 / Burckhardt BC, Burckhardt G - Göttingen, 2005

Skup
Gottinger Transporttage 2005

Mjesto i datum
Göttingen, Njemačka, 03.12.2005. - 04.12.2005

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
brush-border membrane; immunocytochemistry; kidney; sex differences; sodium-glucose cotransporters; steroid hormones

Sažetak
Introduction. SGLT1 mediates a part of glucose and galactose reabsorption in the mammalian proximal tubule (PT). Previous transport studies in isolated brush-border membranes (BBM) from various kidney regions, and hybridization studies in the kidney tissue from rats and rabbits, localized this transporter largely to the PT S3 segments in the outer stripe (OS) and medullary rays (MR). However, due to lack of good antibodies, the detailed localization of SGLT1 along the mammalian nephron has not been resolved. Material and Methods. In this work we used a peptide-specific polyclonal antibody for rat SGLT1 (rSGLT1) and studied the transporter along the nephron of intact and gonadectomized male (M) and female (F) rats, and of sex hormone-treated castrated M rats, by immunoblotting of BBM isolated from the kidney cortex (C) and OS, and by immunocytochemistry in tissue cryosections. These findings were correlated with the phlorizin-sensitive, Na+-dependent uptake of 3H-D-galactose in the BBM vesicles, measured by filter technique, and with the abundance of rSGLT1-specific mRNA in the C and OS tissue, determined by Northern blotting. Results. In immunoblots of BBM from control animals, the antibody labeled a sharp ~40 kDa band, that was not clearly zone- and gender-dependent, and a broad ~75 kDa band, that in both sexes exhibited strong zonal (OS > C) and gender differences (F > M). By immunocytochemistry, the antibody stained strongly brush-border in S3 in the OS and MR and smooth muscles of the blood vessels and renal capsula, and weakly the apical domain of other PT segments in the C. Strong gender differences (F > M) in the staining intensity were observed in S3 in the OS and MR, but not in the blood vessels. The phlorizin-sensitive uptake of 3H-D-galactose in BBM vesicles completely matched the immunoblotting data related to the 75 kDa band and the immunocytochemical staining of brush-border, thus proving zonal and gender differences in the functional transporter. Relevant gender differences (F > M) were also found for the rSGLT1-specific mRNA in the OS. Ovariectomy had no effect, castration caused upregulation, whereas treatment of castrated rats with testosterone, but not with estradiol or progesterone, caused downregulation of the 75 kDa protein and the relevant immunostaining. Conclusions. The data indicate that in the rat kidney the expression of SGLT1 is represented by 75 kDa protein localized largely in the PT S3 segments, where it exhibits gender differences (F > M) at both protein and mRNA level. These gender differences are caused by androgen inhibition.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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