Do estrogen receptor variants explain the enigma of human birth?

During pregnancy progesterone maintains uterine quiescence. In most mammals the onset of labor is precipitated by a fall in circulating levels of progesterone and a rise in plasma concentrations of estrogen which promotes uterine contractile behaviour. In humans, however, progesterone and estrogen concentrations in maternal blood increase progressively across gestation and only fall after the delivery of the placenta. A major enigma has therefore been how is the onset of human labor physiologically regulated with no change in circulating sex steroid concentrations? In the last few years substantial progress has been made in resolving this paradox firstly in relation to progesterone and in this issue of EBioMedicine for estrogen by Anamthathmakula et al. [1]. It seems it all revolves around the receptors for these steroids.