engleski

Rat renal glucose transporter SGLT1 exhibits zonal distribution and androgen-dependent gender differences

SGLT1 (SLC5A1) mediates a part of glucose and galactose reabsorption in the mammalian proximal tubule (PT), but the detailed localization of the transporter along the tubule is still disputable. Here we used several methods to localize the rat SGLT1 (rSGLT1) in the kidneys of intact and variously-treated male (M) and female (F) rats. In immunoblots of isolated renal cortical (C) and outer stripe (OS) brush-border membranes (BBM), a peptide-specific polyclonal antibody for rSGLT1 labeled a sharp, zone- and gender-independent ~40 kDa protein band, and a broad ~75 kDa band, that exhibited strong zonal (OS>C) and gender differences (F>M). In tissue cryosections, the antibody stained strongly BBM of the S3 PT segments in the OS and medullary rays (F>M) and smooth muscles of the blood vessels and renal capsule (F=M), and weakly the apical domain of other PT segments in the C (F~M). The phlorizin-sensitive uptake of 3H-D-galactose in BBM vesicles, as well as the tissue abundance of the rSGLT1-specific mRNA, matched the immunoblotting data related to the 75 kDa band and the immunostaining in S3, proving zonal and gender differences in the functional transporter. Ovariectomy had no effect, castration upregulated, whereas treatment of castrated rats with testosterone, but not with estradiol or progesterone, downregulated the 75 kDa protein and the immunostaining in S3. We conclude 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, that are caused by androgen inhibition.

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

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