Effect of 17β-oestradiol on transepithelial calcium transport in human intestinal-like Caco-2 cells and its interactions with 1,25−dihydroxycholecalciferol and 9-cis retinoic acid

Abstract

Oestrogen therapy helps prevent bone loss in postmenopausal women and corrects a decline in Ca absorption efficiency at the onset of menopause. However, the mechanism by which 17beta-oestradiol (17beta-E2) stimulates Ca absorption is unclear. Oestrogen may exert its effect indirectly via increasing 1,25-dihydroxycholeciferol (1,25 (OH)2D3) or its receptor, or act more directly on the intestines via the oestrogen receptor (OR). Since oestrogen also increases retinol levels, this may influence Ca absorption. To investigate the effect of 17beta-E2 alone and in combination with 1,25 (OH)2D3 on intestinal Ca uptake and absorption in Caco-2 cells cultured under deplete- and replete-9-cis retinoic acid (9-cis RA) conditions. Twenty-one day-old Caco-2 cell monolayers (n 9 wells per treatment) were exposed to 9-cis RA-deplete and -replete media containing dimethyl sulfoxide (control), 10 nM-1,25 (OH)2D3, 10 nM-17beta-E2, or 10 nM-1,25 (OH)2D3 plus 10 nM-17beta-E2, for 48 h. 1,25 (OH)2D3 stimulated Ca uptake, total Ca transport, calbindin D(9K) and CaT1 mRNA levels, while 17beta-E2 and 9-cis RA had no effect on Ca absorption or uptake. Nor did they augment the stimulatory effect of 1,25 (OH)2D3. These in vitro findings suggest that oestrogen does not have a direct effect on intestinal Ca absorption.