Estrogen responsiveness of renal calbindin-D28k gene expression in rat kidney.
In women, calcium excretion in the urine rises after menopause and falls with estrogen replacement therapy. The amount of calcium lost in the urine following estrogen therapy is less than should occur based on changes in serum calcium and the amount of calcium filtered by the kidney. This suggests there may be a direct effect of estrogen therapy to increase renal calcium reabsorption. Calbindin D28k is a putative calcium ferry protein located in the distal renal tubules which has been shown to increase transcellular calcium transport. We proposed that estrogen loss after menopause may diminish gene expression of renal calbindin D28k and subsequently diminish renal calcium reabsorption. We used the ovariectomized rat model of estrogen deficiency to investigate changes at the messenger RNA level of calbindin D28k in ovariectomized 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 D28k. The mRNA levels were approximately three times lower in OVX rats than S-OVX rats. Administration of 17 beta estradiol to OVX rats produced a significant increase in mRNA level to greater than the S-OVX rats by 4 h. Measurement of serum 1,25 dihydroxyvitamin D3 showed lower levels in OVX rats than S-OVX rats but no significant change in E-OVX animals. In conclusion, our results indicate that estrogen increases renal calbindin D28k mRNA levels, by a mechanism independent of changes in 1,25 dihydroxyvitamin D3. This may result in increased expression of calbindin D28k protein which may have a role in reducing renal calcium excretion.
Criddle
R A
RA
Department of Medicine, University of Western Australia, Sir Charles Gairdner Hospital, Perth, Western Australia.
Zheng
M H
MH
Dick
I M
IM
Callus
B
B
Prince
R L
RL
D000818:Animals; D015152:Blotting, Northern; D064092:Calbindin 1; D064026:Calbindins; D002117:Calcitriol / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000235:genetics*
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; D004958:Estradiol; D002117:Calcitriol