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HORMONES AND SIGNALING

Regulation of intestinal NaPi-IIb cotransporter gene expression by estrogen

Departments of Pediatrics and Physiology, Steele Memorial Children's Research Center, University of Arizona Health Sciences Center, Tucson, Arizona 85724

Submitted 15 April 2003 ; accepted in final form 28 July 2003

The current experiments were designed to study the effect of -estradiol on type IIb sodium-coupled phosphate (NaPi-IIb) cotransporter 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 blot analysis indicated that NaPi-IIb mRNA expression was increased by 50% after estrogen treatment. Western blot analysis also detected an increase in BBMV 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.

type IIb sodium-phosphate cotransporter; SLC34A2; Caco-2 cells; rat intestine

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