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Am J Physiol Gastrointest Liver Physiol (July 31, 2003). doi:10.1152/ajpgi.00172.2003
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Submitted on April 15, 2003
Accepted on July 28, 2003

Regulation of Intestinal NaPi-IIb Cotransporter Gene Expression by Estrogen

Hua Xu1, Jennifer K. Uno1, Michael Inouye1, Liping Xu1, Jason B. Drees1, James F. Collins1, and Fayez K. Ghishan1*

1 Department of Pediatrics and Physiology, University of Arizona Health Sciences Center, Steele Memorial Children's Research Center, Tucson, AZ, USA

* To whom correspondence should be addressed. E-mail: fghishan{at}peds.arizona.edu.

The current experiments were designed to study the effect of {beta}-estradiol (E2) on NaPi-IIb gene expression. Uptake studies with intestinal brush-border membrane vesicles (BBMV) showed that estrogen treatment increased sodium-dependent phosphate absorption by ~ 45% in rat intestine. Northern blotting indicated that NaPi-IIb mRNA expression was increased by ~ 50% after estrogen treatment. Western blot analysis also detected an increase in BBM NaPi-IIb protein expression in estrogen-treated rats. In human intestinal Caco-2 cells, NaPi-IIb mRNA abundance was increased ~ 60% after estrogen treatment, and this increase could be abolished by inhibition of gene transcription. Transfection studies with human NaPi-IIb promoter reporter constructs showed that the promoter was responsive to estrogen treatment. These studies demonstrate for the first time that estrogen stimulates intestinal sodium-dependent phosphate absorption in female rats. This stimulation is associated with increased NaPi-IIb mRNA and protein expression. Thus, the effect of estrogen on intestinal Pi absorption may be partially due to activation of NaPi-IIb gene transcription.




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