GnH in the placenta shows its highest expression in the first trimester (Siler-Khodr, 1978, 1988). Interestingly, it is found in cytotrophoblasts, but not syncytiotrophoblast. Pla centa-derived GnRH functions to regulate trophoblast hCG ofMMP-2 and MMP-9 (Peng, 2016). Placenta-derived GnRH is also the likely cause of elevated maternal GnRH levels in pregnancy (Siler-Khodr, 1984).
CH is a member of a larger family of CRH-related pep tides that includes CRH and urocortins (Dautzenberg, 2002).
Maternal serum CRH levels increase from 5 to 10 pmollL in the nonpregnant woman to approximately 100 pmollL in the early third trimester of pregnancy and to almost 500 pmollL abruptly during the last 5 to 6 weeks (see Fig. 5-18). Urocortin also is produced by the placenta and secreted into the maternal circulation, but at much lower levels than seen for CRH (Flo rio, 2002). After labor begins, maternal plasma CRH levels rise even further (Petraglia, 1989, 1990).
he biological function of CRH synthesized in the placenta, membranes, and decidua has been somewhat deined. CRH receptors are present in many tissues including placenta. Trophoblast, amniochorion, and decidua express both CRH-R1 and CRH-R2 receptors and several variant receptors (Florio, 2000). Both CRH and urocortin enhance trophoblast secretion of adrenocorticotropic hormone (ACTH), supporting an autocrine-paracrine role (Petraglia, 1999). Large amounts of trophoblast CRH enter maternal blood.
Other proposed biological roles include induction of smooth-muscle relaxation in vascular and myometrial tissue and immunosuppression. The physiological reverse, however, induction of myometrial contractions, has been proposed for the rising CRH levels seen near term. One hypothesis suggests that CRH may be involved with parturition initiation (Wadhwa, 1998). Some evidence suggests that urocortin 2 expression is induced at term and induces expression of pro inlammatory markers and prostaglandin F receptor expression in the placenta and myometrium (Voltolini, 2015). Prostaglandin formation in the placenta, amnion, chorion laeve, and decidua is increased with CRH treatment Oones, 1989b). hese observations further support a potential action in parturition timing.
Glucocorticoids act in the hypothalamus to inhibit CRH release, but in the trophoblast, glucocorticoids stimulate CRH gene expression Oones, 1989a; Robinson, 1988). hus, there may be a novel positive feedback loop in the placenta by which placental CRH stimulates placental ACTH to stimulate fetal and maternal adrenal glucocorticoid production with quent stimulation of placental CRH expression (Nicholson, 2001; Riley, 1991).
Growth hormone-releasing hormone has an unknown role (Berry, 1992). Ghrelin is another regulator of hGH secretion that is produced by placental tissue (Horvath, 2001). Trophoblast ghrelin expression peaks at midpregnancy and is a paracrine regulator of diferentiation or is a potential regulator of human growth hormone variant production, described next (Fuglsang, 2005; Gualillo, 2001).