Weak direct proliferative action of estradiol on human endometrial cells in culture

Since the recognition by Berthois et al. (1986) that phenol red, a pH indicator in culture media, has a weak estrogenic action on breast cancer cells, all previous experiments reporting a lack of mitogenic activity of estrogens in culture were thought to be artefactual, due to the presence of phenol red. With fifteen primary cultures of normal human endometrial cells realized in phenol red free medium we looked at the addition of phenol red and estradiol. Phenol red has a weak mitogenic activity inducing a 20-40% increase in cell number, showing that normal endometrial cells are less sensitive than breast cancer cells. Estradiol also exerts a mitogenic activity with 15-25% more cells, an increase slightly lower than that induced by phenol red. But such an activity can be observed only in the absence of insulin in the medium and the presence of 10% steroid depleted fetal calf serum. If any of these conditions are not respected, estradiol has no effect on cell multiplication. So it can be concluded that estradiol has a weak direct mitogenic activity on human endometrial cells in culture, but this activity is quantitatively beyond measure with the proliferation triggered in vivo by estrogens during the estrous cycle.