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1 Unit of Molecular Toxicology, Institute for Medical Reseach and Occupational Health, Zagreb, -, Croatia (Hrvatska)
2 Department of Physiology and Pathophysiology, Georg-August University of Goettingen, Goettingen, -, Germany
3 Department of Physiology and Pathophysiology, Kyorin University School of Medicine, Tokyo, -, Japan
* To whom correspondence should be addressed. E-mail: sabolic{at}imi.hr.
In rats, the secretion of p-aminohippurate (PAH) by the kidney is higher in males (M) than in females (F). A role of the major renal PAH transporters, OAT1 and OAT3, in generation of these gender differences, as well as the responsible hormones and mechanisms, have not been clarified. Here we used various immunocytochemical methods to study effects of gender, gonadectomy, and treatment with sex hormones on localization and abundance of OAT1 and OAT3 along the rat nephron. Both transporters were localized to the basolateral membrane: OAT1 was strong in proximal tubule S2 and weak in the S3 segments, whereas OAT3 was stained in proximal tubule S1 and S2 segments, thick ascending limb, distal tubule, and in principal cells along the collecting duct. Gender differences in the expression of both transporters in adult rats (M>F) were observed only in the cortical tubules. OAT1 in the cortex was strongly reduced by castration in adult M, whereas the treatment of castrated M with testosterone, estradiol or progesterone resulted in its complete restitution, further depression, or partial restitution, respectively. In adult F, ovariectomy weakly increased, whereas the estradiol treatment of ovariectomized F strongly decreased the expression of OAT1. The expression of OAT3 in the M and F cortex largely followed a similar pattern, except ovariectomy and progesterone treatment showed no effect, whereas in other tissue zones gender differences were not observed. In prepubertal rats, the expression of OAT1 and OAT3 in the kidney cortex was low, and showed no sex differences. Our data indicate that gender differences in the rat renal cortical OAT1 and OAT3 (M>F) appear after puberty, and are determined by both a stimulatory effect of androgens (and progesterone in case of OAT1), and an inhibitory effect of estrogens.
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