title: Rat renal cortical OAT1 and OAT3 exhibit gender differences determined by both androgen stimulation and estrogen inhibition.
abstract: In rats, the secretion of p-aminohippurate (PAH) by the kidney is higher in males (M) than in females (F). The role of the major renal PAH transporters, OAT1 and OAT3, in the generation of these gender differences, as well as the responsible hormones and mechanisms, has 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 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 that 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 gender 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 the case of OAT1) and an inhibitory effect of estrogens.
authors.affiliation: Unit of Molecular Toxicology, Institute for Medical Research and Occupational Health, HR-10001 Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Ljubojevic
authors.forename: Carol M
authors.initials: CM
authors.lastname: Herak-Kramberger
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Hagos
authors.forename: Andrew
authors.initials: A
authors.lastname: Bahn
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endou
authors.forename: Gerhard
authors.initials: G
authors.lastname: Burckhardt
authors.forename: Ivan
authors.initials: I
authors.lastname: Sabolic
mesh_terms: D000818:Animals; D001692:Biological Transport; D002369:Castration / Q000662:veterinary; D002462:Cell Membrane / Q000502:physiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000254:growth & development* / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D008297:Male; D027362:Organic Anion Transport Protein 1 / Q000494:pharmacology*; D029362:Organic Anion Transporters, Sodium-Independent / Q000494:pharmacology*; D010052:Ovariectomy / Q000662:veterinary; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors
chemical_list: D012739:Gonadal Steroid Hormones; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C421043:Slc22a6 protein, rat; C114338:organic anion transport protein 3; D011374:Progesterone