The species differences in hormonal regulation of progenitor cells may be due to the inherent differences in circulating levels and hormonal cycles that differ between species. During puberty in the mouse, Betamipron estrogen is responsible for maturation of the mammary gland by mediating ductal elongation through mitogenic actions on stem/progenitor cells. Although estrogen is known to promote proliferation of human breast cancer cells, proliferation of normal cells within the human gland is not at its peak during the follicular phase, when circulating estrogens are at their maximum, but rather are maximal during the luteal phase, when the ratio of circulating progesterone to estrogen is increased. Uniquely, the human corpus luteum secretes estrogen in addition to progesterone, and tamoxifen administration can inhibit breast epithelial proliferation during the luteal phase of the menstrual cycle, suggesting that both estrogen and progesterone regulate progenitor activity in the human breast. This difference in estrogen to progesterone ratios during hormone cycles as well as differences in circulating estrogen levels may have important consequences in the regulation of stem/ progenitor cells in higher mammals. Amoxapine Despite the differences in the progenitor specific to hormonal responses, several similarities in progenitor cell regulation were observed between mice and humans. Combination estrogen and progesterone stimulated maximum stem/progenitor cell expansion, which has also been observed in rodents. Likewise, our studies reveal that WNT ligand receptor LRP6 is expressed by luminal epithelial cells and functionally contributes to the expansion of luminal acinar colonies. This pathway is a major regulator of mammary stem cells in mice. Proliferation and expansion of progenitor cells occurs through a RANKL-mediated pathway through luminal RANK expression. Furthermore, our findings revealed that TBX3 coordinates a non-hormonal expansion of both acinar and ductal progenitor cells by inducing paracrine WNT signaling. TBX3 regulation of WNT signaling has also been observed in mice.