ABSTRACT
In an adult mammal, the uterus undergoes waves of cell proliferation, differentiation, and remodeling in preparation to receive a blastocyst.These processes are under the overall regulation of ovarian sex steroid hormones that act through their transcription factor receptors. In the most commonly studied species, rats and mice, adult animals have an estrous cycle that is without a true luteal phase and is, therefore, dominated by estradiol-17β (E2). Only very small amounts of progesterone (P4) are synthesized before ovulation and much of what is synthesized is largely converted in situ to 20α-hydroxyprogesterone, an inactive metabolite.1 Nevertheless, the small increase in circulating P4 levels is required to enhance the positive feedback of E2 in the hypothalamus to cause the luteinizing hormone (LH) surge that induces ovulation, thereby synchronizing fertilization with the uterine preparation for implantation that, in the mouse, occurs 4.5 days later. If copulation occurs, the corpora lutea are maintained and P4 synthesis continues, causing differentiation of the uterus and a switch in sensitivity to E2stimulated cell proliferation from the epithelium to the stroma in preparation for blastocyst implantation. In contrast to species with estrous cycles, Old-World primates have a luteal phase that follows ovulation, P4 continues to be synthesized, and the stromal cells begin to decidualize.2 If pregnancy does not occur, chorionic gonadotropin is not available to maintain P4 synthesis, and the uterine
lining is sloughed off during menstruation followed by cell proliferation to replenish the lost functionalis layer. These two extremes of hormonal control over uterine cell proliferation are discussed in this chapter.
