The Endocrinology of Late Pregnancy and Parturition

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The establishment, maintenance, and termination of pregnancy is dependent on endocrine and paracrine interactions among the mother, the fetus, and the placenta. Progesterone and estrogens, produced by the feto-placental unit, promote and hinder, respectively, the maintenance of the pregnancy. In several species including the sheep, the maturation of the fetal hypothalamo-pituitary-adrenal axis at term results in elevated fetal cortisol level that causes an increase in the ratio of estrogens to progesterone in the maternal circulation, initiating parturition. Local and diurnal, but not systemic and sustained, increases of the estrogen:progesterone ratio may have a similar function in primates including women. Prostaglandins, synthesized in the gestational tissues may facilitate myometrial activity, cervical maturation, and membrane rupture and thus be of crucial importance as paracrine factors effecting labor onset. Locally produced as well as pituitary oxytocin is a powerful stimulant of myometrial contractions in late pregnancy. Proinflammatory cytokines are likely responsible for early labor in the setting of intrauterine infection. An elevated TH2:TH1 cytokine ratio is part of the mechanism responsible for the immune tolerance of the fetal allograft by the mother. The trophoblast produces a diversity of hormonal peptides and proteins, such as hCG, CRH, GnRH, ACTH, and chorionic somatomammotropin, the function of which is unclear at late gestation. Endothelin, relaxin, prolactin, catecholamines, and growth factors are also present in the late pregnant uterus, but their roles in labor onset remain to be established.