The exact role of estrogen in regulation of human uterine quiescence and cervical competency is less well understood. hat said, estrogen can advance progesterone responsiveness and, in doing so, promote uterine quiescence. At the end of pregnancy, estrogen aids processes that mediate uterine activation and cervical ripening.
Both progesterone and estrogen bind to nuclear receptors that regulate gene transcription in a cell-and context-speciic pattern. Two nuclear receptors for estrogen are estrogen receptor a (ERa) and estrogen receptor 3 (ER3). Nuclear receptor isoforms of the progesterone receptor (PR-A and PR-B) are encoded by difering transcripts from a single gene (Patel, 2015).
Prostaglandins are lipid molecules with varied hormone-like actions. In parturition, they playia prominent role in myometrial contractility, relaxation, and inlammation. Prostaglandins interact with a family of eight diferent G-protein-coupled receptors (p. 406), several of which are expressed in myometrium and cervix (Konopka, 2015; Myatt, 2004).
The major synthetic pathways involved in prostaglandin biosynthesis are shown in Figure 21-2. Prostaglandins are produced using plasma membrane-derived arachidonic acid, which usually is released by the action of phospholipase A2 or C. Arachidonic acid can then act as substrate for both type 1 and 2 prostaglandin H synthase (PGHS-l and -2), which are also called cyclooxygenase-l and -2 (COX-l and -2). Both PGHS isoforms convert arachidonic acid to the unstable prostaglandin G2 and then to prostaglandin H2. hese enzymes are the target of many nonsteroidal antiinlammatory drugs (NSAIDs). Indeed, the tocolytic actions of speciic NSAIDs, as discussed in Chapter 42 (p. 826), were considered promising until they were shown to have adverse fetal efects (Loudon, 2003; Olson, 2003, 2007).
Through prostaglandin isomerases, prostaglandin H2 is converted to active prostaglandins. These include prostaglandins E2 (PGEJ, F2x (PGF2x), and 12 (PGI2). Isomerase expression is tissue-speciic and thereby controls the relative production of various prostaglandins. Another important control point for prostaglandin activity is its metabolism, which most often is
Phospholipase C with through the action of 15-hydroxyprostaglandin dehydrogenase (PGDH). Expression of this enzyme is up regulated during pregnancy in the uterus and cervix, which provides the important ability to rapidly inactivate prostaglandins (Giannoulias, 2002; Kishore, 2014). Thus, myometrial responses to prostaglandins stem from a balance between prostaglandin synthesis versus metabolism, from the relative expression of various prostaglandin receptors, or from a switch in receptor-signaling pathways (Kandola, 2014; Lyall, 2002; Olson, 2007; Smith, 2001). It is entirely possible that prostanoids contribute to myometrial relaxation at one stage of pregnancy and to myometrial contractions after parturition initiation (Myatt, 2004).