Commentary Fine Tuning of Endometrial Function by Estrogen and Progesterone Through microRNAs

The endometrium is a complex steroid-responsive tissue that undergoes cyclic proliferation, hypertrophy, and differentiation in anticipation of embryo implantation. In the human, when pregnancy does not occur, menstrual shedding is followed by healing and intense proliferation in response to circulating estrogen resulting from ovarian follicular development. After ovulation, progesterone is secreted from the newly formed corpus luteum, transforming the endometrium into a secretory structure and establishing receptivity toward the nascent embryo, precisely and synchronously timed around a window of implantation [1]. Delays in the developmental milestones of the endometrium [2] can lead to infertility or pregnancy loss. Moreover, imbalance between the actions of estrogen and progesterone are associated with abnormal uterine bleeding [3] and proliferative disorders, such as endometriosis and endometrial hyperplasia [4]. Proges-terone is essential for the establishment of pregnancy [5], opposing the actions of estrogen by a remarkable number of different mechanisms. One recognized antiestrogenic action of progesterone in the endometrium is the regulation of the cognate receptors for estrogen and progesterone [6]. Although estrogen increases the concentration of its own receptor (ESR1) and that of progesterone (PGR), progesterone downregulates the availability of ESR1 in most endometrial cell types and reduces its own receptor in the glandular epithelium. The reduction in steroid receptors is one of many means by which progesterone limits the action of estrogen during the secretory phase of the normal menstrual cycle.