Regulation Of Estrogen For Duodenal Calcium Absorption And Its Mechanism

Objective: Intestinal calcium absorption from the diet is an essential process maintaining calcium balance and bone health.Estrogen has an important physiological and pathological significance in the human body.The previous studies suggested that estrogen is involved in the regulation of intestinal calcium absorption.However,the mechanisms of estrogen action in the regulation of intestinal calcium absorption have not been completely understood.In this study,we aimed at determining effect of estrogen on duodenal calcium absorption and further exploring the mechanisms by which estrogen regulates duodenal calcium absorption.These data may provide the basis for the development of therapeutic strategies to manage some clinical diseases.Methods: The studies were performed in six-week-old C57 BL / 6J female mice and human duodenal epithelial cells,SCBN cells.The mice were ovariectomized(OVX)or sham-operated.OVX mice were randomly assigned to OVX and OVX + 17?-estradiol(E2)groups at two weeks after operation.The sham-operated mice were served as the control group.17?-estradiol(10.5 ?g/100 g body weight)was administrated in OVX + E2 group.Murine duodenal calcium absorption was measured by using single pass perfusion of the duodenum in vivo.The calcium absorption of SCBN cells was evaluated by PTI calcium imaging system.The expression of calcium transport proteins,transient receptor potential cation channel(TRPV6)and plasma membrane calcium pump(PMCA1b),in the duodenum or SCBN cells were systematically studied.Result: 1.Compared with the control group,the duodenal calcium absorption in OVX mice was significantly decreased,which returned to control level after 17?-estradiol treatment(P<0.05).2.The expressions of calcium transport proteins,TRPV6 and PMCA1 b,in the duodenal mucosa of OVX mice was markedly decreased,and 17?-estradiol treatment up-regulated the expressions of TRPV6 and PMCA1 b in OVX mice(P<0.05).3.The results from SCBN cells showed that 17?-estradiol treatment increased the calcium influx and upregulated the expressions of TRPV6 and PMCA1 b in SCBN cells(P<0.05).4.TRPV6 and PMCA1 b inhibitor significantly reduced the calcium influx in SCBN cells(P<0.05).5.Selective ER? agonist,PPT,increased calcium influx in SCBN cells through TRPV6,whereas selective ER? agonist,DPN,increased calcium influx in SCBN cells through PMCA1b(P<0.05).6.Estrogen receptor alpha(ER?)inhibitor or ER? sh RNA decreased the expression of TRPV6 in SCBN cells,but did not change the expression of PMCA1 b.Estrogen receptor beta(ER?)inhibitor or ER? sh RNA reduced the expression of PMCA1 b in SCBN cells,but did not change the expression of TRPV6(P<0.05).Conclusion: Estrogen regulates duodenal calcium absorption through differential roles of ER? and ER? on TRPV6 and PMCA1 b in duodenal epithelial cells,which contributes to elucidate further the mechanism of estrogen action in the intestine.