Placental production of protein hormones

The placenta is a very rich source of both protein and steroid hormones, only a few of which are unique to pregnancy (Fig. 18.1). These placental hormones are responsible for almost all the maternal and some of the fetal adaptations to pregnancy.

Human chorionic gonadotropin

Human chorionic gonadotropin (hCG) is a dimeric protein hormone whose structure is closely related to luteinizing hormone (LH) (Chapter 1). It is among the earliest products of the trophoblast cells of the embryo and is necessary to signal the maternal organism that conception has occurred. β-hCG mRNA can be detected in an eight-cell embryo, although intact hCG is not detectable in the maternal bloodstream or urine until 6 days after fertilization. hCG secretion is quantitatively related to the total mass of trophoblast in the placenta. Its concentration in the maternal serum approximately doubles every 2–3 days in early pregnancy; this can be used as a screen to differentiate normal from abnormal pregnancies. Failure of the hCG concentrations to increase appropriately may indicate an abnormal implantation such as an ectopic (tubal) pregnancy or a nonviable intrauterine gestation. Higher than expected levels of hCG are seen with multiple gestations (Chapter 35) and molar pregnancies (Chapter 45).

The major biologic role of hCG is to “rescue” the corpus luteum of the ovary from its programmed demise 12–14 days after ovulation. Because of the close structural relationship of hCG to LH, hCG is able to bind to the LH receptor on luteal cells. hCG can therefore substitute for LH, supporting the corpus luteum when a pregnancy is present. Maintenance of the corpus luteum allows continued secretion of ovarian progesterone after day 14 postovulation and maintenance of the early pregnancy. Surgical removal of the corpus luteum without progesterone supplementation before the 9th menstrual week of pregnancy will result in a pregnancy loss. Administration of an antiprogestin such as RU-486 will have similar results. By 9 weeks’ gestation (7 weeks after conception), the placenta has typically acquired sufficient cellular mass to supply the large amounts of progesterone necessary for pregnancy maintenance. Progesterone production is taken over by the placenta at this point and the corpus luteum could be removed without adverse effect on pregnancy maintenance. At the end of the first trimester, hCG also stimulates the fetal gonads to make the steroid hormones responsible for differentiation of the internal and external genitalia (Chapters 5 and 6).

Many of the hormones produced within the placenta result from a two-cell system that mimics the interactions between the neuroendocrine hypothalamus and the pituitary gland (Fig. 18.2a). For instance, gonadotropin-releasing hormone (GnRH) can be synthesized and secreted by the cytotrophoblast cells of the placenta. GnRH from the cytotrophoblast stimulates hCG production by the syncytiotrophoblast. As pregnancy progresses and the placenta becomes the major site of progesterone production, hCG’s primary role changes from maintenance of the corpus luteum to maintenance of progesterone production by the syncytiotrophoblast. The serum level of hCG reflects this change by increasing to a maximum at about the 9th or 10th menstrual week of pregnancy and then decreasing to a much lower steady state level for the remainder of the pregnancy.