Mawieh Hamad, Jasmine Shafarin and Jagan Sundaram
The Sharjah Institute for Medical Research, University of Sharjah, P O Box 27272, Sharjah, UAE
It is well-established that elevated levels of estrogen (17-β estradiol, E2) in premenopausal women associate with increased serum iron availability mostly through E2's ability to downregulate hepcidin synthesis. Since release of recycled iron represents the main source of systemic iron, it is possible that E2 increases systemic iron availability at the expense of intracellular iron stores in iron storing cells like macrophages. This implies that exposure of E2-responsive mononuclear cells to E2 may deplete their intracellular (exchangeable) iron stores. To test this hypothesis, ER-α+ MCF-7 cells treated with E2 at 5-20nM and cultured for 6-24 hours were assessed for intracellular iron status and the expression of hepcidin, ferroportin and transferrin receptor (CD71). E2 treatment (10nM and 20nM concentration for 12 and 24 hours) resulted in a significant decrease in hepcidin synthesis and a noticeable increase in ferroportin and CD71 expression both at the mRNA and protein levels. Furthermore, MCF-7 cells treated with 10nM E2 for 12 or 24 hours, showed a significant reduction in intracellular iron concentration as compared with untreated cells. These findings clearly suggest that E2 enhances intracellular iron depletion. This could, at least partially, explain the anti-carcinogenic effects of E2 as E2-mediated reduction in intracellular iron availability is likely to associate with reduced proliferative activity and diminished intracellular oxidative stress.