Figure 1.

Estradiol promotes hematopoietic stem cell (HSC) self-renewal.

In female mice, HSC proliferation is augmented by circulating estradiol (E2), which is produced from the ovaries during reproductive years, and at higher levels from the placenta during pregnancy. E2 binds to the estrogen receptor-α (ER-α, green), which upon dimerization is translocated to the nucleus and enhances the expression of target genes involved in HSC proliferation (top left panel). Interrupting this pathway by ovariectomy (1), by the administration of an aromatase inhibitor that blocks the production of estradiol from its precursors (2), or by genetic disruption of Esr1, the gene encoding for ER-α (3), leads to reduced basal proliferation rate of HSC in females (top right panel). In males, despite the expression of ER-α in HSC, paucity of estradiol determines a lower basal HSC proliferation rate (bottom right panel). However, exogenous administration of E2 or ER-α agonists can induce an increase in HSC self-renewal also in males as well (bottom right panel).