ESTROGEN RESPONSIVENESS OF RENAL CALBINDIN-D-28K GENE-EXPRESSION IN RAT-KIDNEY

In women, calcium excretion in the urine rises after menopause and fal ls with estrogen replacement therapy. The amount of calcium lost in th e urine following estrogen therapy is less than should occur based on changes in serum calcium and the amount of calcium filtered by the kid ney. This suggests there maybe a direct effect of estrogen therapy to increase renal calcium reabsorption. Calbindin D-28k is a putative cal cium ferry protein located in the distal renal tubules which has been shown to increase transcellular calcium transport. We proposed that es trogen loss after menopause may diminish gene expression of renal calb indin D-28k and subsequently diminish renal calcium reabsorption. We u sed the ovariectomized rat model of estrogen deficiency to investigate changes at the messenger RNA level of calbindin D-28k in ovariectomiz ed rats (OVX), sham ovariectomized rats (S-OVX), and estrogen treated ovariectomized rats (E-OVX). We have demonstrated that ovariectomy in rats diminishes the gene expression of renal calbindin D-28k. The mRNA levels were approximately three times lower in OVX rats than S-OVX ra ts. Administration of 17 beta estradiol to OVX rats produced a signifi cant increase in mRNA level to greater than the S-OVX rats by 4 h. Mea surement of serum 1,25 dihydroxyvitamin D-3 showed lower levels in OVX rats than S-OVX rats but no significant change in E-OVX animals. In c onclusion, our results indicate that estrogen increases renal calbindi n D-28k mRNA levels, by a mechanism independent of changes in 1,25 dih ydroxyvitamin D-3. This may result in increased expression of calbindi n D-28k protein which may have a role in reducing renal calcium excret ion. (C) 1997 Wiley-Liss, Inc.