Progesterone maintains uterine quiescence in part by mechanisms that lower expression of various key proteins needed for contractility. hese contraction-associated proteins (CAPs) include the oxytocin receptor, prostaglandin F receptor, and connexin-43. At the end of pregnancy, increased stretch along with greater estrogen dominance raises CAP levels. Integration ofdiverse regulatory pathways culminates in released inhibition ofconnexin-43 and oxytocin receptor levels to promote greater uterine contractility (Nadeem, 2016; Renthal, 2010; Williams, 2012b).
As another potential mechanism, progesterone maintains uterine quiescence through support of myometrial caspase 3, which is an anticontractile agent Qeyasuria, 2009). his protein degrades both actin and the speciic gap junction protein, connexin-43 (Kyathanahalli, 2015).
called connexins. Six connexins form a hemichannel (connexon), nel. Connexons and gap junction channels can be formed from one or more connexin proteins. The composition of the gap junc tion channel is important for these channels' selectivity with regard to passage of molecules and communication between cells.
In mice, myometrial caspase 3 activation is regulated by a pregnancy-induced endoplasmic reticulum stress response (ERSR). As background, the endoplasmic reticulum aids protein folding and transport. Functional irregularities cause misfolded proteins to accumulate and trigger the ERSR. he ERSR and its unolded-protein response (UPR) are cellular mechanisms that work to maintain homeostasis in the face of stimuli, such as stretch and inlammation. Prolonged ERSR promotes caspase 3 activation to preserve quiescence despite these stimuli.
Various cell surface receptors directly regulate myocyte contractility. Discussions thus far have described ion channel-linked receptors that regulate intracellular Ca2+ and membrane potential. In addition, numerous G-protein-coupled receptors appear to be modified during the phases of parturition. Several of these are present in myometrium and associated with Gos-mediated activation of adenylyl cyclase to yield higher cAMP levels. These receptors together with appropriate ligands may act with sex steroid hormones to maintain uterine quiescence (Price, 2000; Sanborn, 1998). Examples are the LH receptor and corticotropin-releasing hormone receptor 1 (CRHR1), both described in this section (Fig. 21-8). Other G-protein-coupled myometrial receptors, instead, are associated with G-protein-mediated activation of phospholipase C, which remember releases arachidonic acid. Ligands for the G-protein-coupled receptors include numerous neuropeptides, hormones, and autacoids. Many of these are available to the myometrium during pregnancy in high concentration via endocrine or autocrine mechanisms.
3-Adrenoreceptors are prototypical examples of cAMP signaling causing myometrium relaxation. 3-Adrenergic receptors mediate Gs-stimulated increases in adenylyl cyclase, elevated