Gender difference in the Oatp1-mediated tubular reabsorption of estradiol 17beta-D-glucuronide in rats.
The gender difference in the urinary excretion of estradiol-17beta-glucuronide (E(2)-17betaG) was examined in rats. The urinary clearance of E(2)-17betaG was >250 times lower in male than in female rats. No such major gender difference was observed in its biliary excretion or metabolism in kidney homogenate. Both plasma protein binding and inulin clearance were comparable in male and female rats, suggesting that this gender difference cannot be explained by glomerular filtration. The urinary clearance with respect to the plasma unbound E(2)-17betaG in male rats was <1% of the glomerular filtration rate, indicating its potential reabsorption by the kidney, and this increased to a level comparable with that found in female rats when dibromosulfophthalein was coinfused. A marked increase in E(2)-17betaG urinary excretion was also observed in male rats that had undergone orchidectomy. Testosterone injections given to female rats reduced the urinary excretion to a level comparable with that of control male rats. The concomitant change in the expression of the gene product for organic anion-transporting polypeptide Oatp1, of which E(2)-17betaG is a typical substrate, was found in the kidney membrane fractions after these treatments. These results suggest that urinary E(2)-17betaG excretion is subject to hormonal regulation and that the large gender difference can be explained by regulation in Oatp1-mediated reabsorption.
Gotoh
Yasumasa
Y
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Kato
Yukio
Y
Stieger
Bruno
B
Meier
Peter J
PJ
Sugiyama
Yuichi
Y
D000042:Absorption; D000818:Animals; D001646:Bile / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D015870:Gene Expression; D005919:Glomerular Filtration Rate; D020719:Glucuronides / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology
D001798:Blood Proteins; D020719:Glucuronides; D029362:Organic Anion Transporters, Sodium-Independent; C421102:Slco1a1 protein, rat; D013739:Testosterone; D004958:Estradiol