The relationship between estrogen and some types of breast cancer has been clearly established. However, although several studies have demonstrated the relationship between estrogen and glucose uptake via phosphatidylinositol 3-kinase (PI3K)/Akt in other tissues, not too much is known about the possible cross talk between them for development and maintenance of breast cancer. This study was designed to test the rapid effects of 17β-estradiol (E2) or its membrane-impermeable form conjugated with BSA (E2BSA) on glucose uptake in a positive estrogen receptor (ER) breast cancer cell line, through the possible relationship between key components of the PI3K/Akt signaling pathway and acute steroid treatment. MCF-7 human breast cancer cells were cultured in standard conditions. Then 10 nM E2 or E2BSA conjugated were administered before obtaining the cell lysates. To study the glucose uptake, the glucose fluorescent analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose was used. We report an ER-dependent activation of some of the key steps of the PI3K/Akt signaling pathway cascade that leads cells to improve some mechanisms that finally increase glucose uptake capacity. Our data suggest that both E2 and E2BSA enhance the entrance of the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose, and also activates PI3K/Akt signaling pathway, leading to translocation of glucose transporter 4 to the plasma membrane in an ERα-dependent manner. E2 enhances ER-dependent rapid signaling triggered, partially in the plasma membrane, allowing ERα-positive MCF-7 breast cancer cells to increase glucose uptake, which could be essential to meet the energy demands of the high rate of proliferation.

The mechanism for the development of insulin resistance in normal pregnancy is complex and is associated with serum levels of both progesterone and 17beta-estradiol. However, it remains unclear whether estrogens alone or progestins alone can cause insulin resistance, or whether it is a combination of both which produces this effect. We attempted to determine the role played by progesterone and/or 17beta-estradiol on the phenomena of sensitivity to insulin action that take place during pregnancy in the rat. Ovariectomized rats were treated with different doses of progesterone and/or 17beta-estradiol in order to simulate the plasma levels in normal pregnant rats. A euglycemic/hyperinsulinemic clamp was used to measure insulin sensitivity. At days 6 and 11, vehicle (V)- and progesterone (P)-treated groups were more insulin resistant than 17beta-estradiol (E)- and 17beta-estradiol+progesterone (EP)-treated groups. Nevertheless, at day 16, the V, EP and E groups were more resistant to insulin action than the P group. On the other hand, the V, EP and E groups were more insulin resistant at day 16 than at day 6, whereas the P group was more insulin resistant at day 6 than at day 16. Our results seem to suggest that the absence of female steroid hormones gives rise to a decreased insulin sensitivity. The rise in insulin sensitivity during early pregnancy, when the plasma concentrations of 17beta-estradiol and progesterone are low, could be due to 17beta-estradiol. However, during late pregnancy when the plasma concentrations of 17beta-estradiol and progesterone are high, the role of 17beta-estradiol could be to antagonize the effect of progesterone, diminishing insulin sensitivity.