Progesterone control of myometrial contractility

During pregnancy, the primary function of the uterus is to be quiescent and not contract, which allows the growing fetus to develop and mature. A uterine muscle layer, myometrium, is composed of smooth muscle cells (SMCs). Before the onset of labor contractions, the uterine SMCs experience a complex biochemical and molecular transformation involving the expression of contraction-associated proteins. Labor is initiated when genes in SMCs are activated in response to a combination of hormonal, inflammatory and mechanical signals. In this review, we provide an overview of molecular mechanisms regulating the process of parturition in humans, focusing on the hormonal control of the myometrium, particularly the steroid hormone progesterone. The primary reason for discussing the regulation of myometrial contractility by progesterone is the importance of the clinical problem of preterm birth. It is thought that the hormonal mechanisms regulating premature uterine contractions represent an untimely triggering of the normal events occurring during term parturition. Yet, our knowledge of the complex and redundant hormonal pathways controlling uterine contractile activity leading to delivery of the neonate remains incomplete. Finally, we introduce recent animal studies using a novel class of drugs, Selective Progesterone Receptor Modulators, targeting progesterone signaling to prevent premature myometrial contractions.