Regulation of intestinal NaPi-IIb cotransporter gene expression by estrogen.
The current experiments were designed to study the effect of beta-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 approximately 45% in rat intestine. Northern blot analysis indicated that NaPi-IIb mRNA expression was increased by approximately 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 approximately 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.
Xu
Hua
H
Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA.
Uno
Jennifer K
JK
Inouye
Michael
M
Xu
Liping
L
Drees
Jason B
JB
Collins
James F
JF
Ghishan
Fayez K
FK
D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D005973:Glutamine / Q000493:pharmacokinetics; D006801:Humans; D007150:Immunohistochemistry; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism / Q000648:ultrastructure; D008871:Microvilli / Q000378:metabolism / Q000648:ultrastructure; D010710:Phosphates / Q000493:pharmacokinetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050608:Sodium-Phosphate Cotransporter Proteins; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D027981:Symporters / Q000235:genetics* / Q000378:metabolism
D004967:Estrogens; D010710:Phosphates; D012333:RNA, Messenger; C493557:SLC34A2 protein, human; C493559:Slc34a2 protein, rat; D050608:Sodium-Phosphate Cotransporter Proteins; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D027981:Symporters; D005973:Glutamine; D004958:Estradiol