Steroid hormone production during pregnancy requires cooperation among maternal, fetal and placental organs and enzyme pathways (Fig. 19.1a). The fetus and the placenta each lack key steroidogenic enzymes and would be unable to synthesize certain steroid molecules if they existed in isolation. Interplay among fetus, placenta and the mother are essential to produce the full spectrum of steroidal products necessary for pregnancy maintenance. For example, the fetal adrenal gland has diminished 3β-hydroxysteroid dehydrogenase: Δ4–5 isomerase activity and therefore it secretes large amounts of the progesterone precursors, pregnenolone and dehydroepiandrosterone, and very little progesterone (Chapter 2). Because the fetus can synthesize so very little progesterone directly, it obtains its supplies from the placenta. Because the syncytiotrophoblast layer of the placenta lacks a key enzyme, it cannot synthesize cholesterol from circulating acetate. To synthesize progesterone, the placenta requires cholesterol or pregnenolone from maternal or fetal sources. The vast majority arises from the maternal system and is transported to the placenta in the form of low density lipoprotein (LDL) cholesterol.
In contrast to the mother and placenta, the fetus has a remarkable ability to rapidly conjugate steroids with sulfates. Sulfation creates less potent steroids with more rapid clearance, characteristics that allow the fetus to be safely exposed to the high levels of circulating steroids seen during pregnancy. The fetal liver can efficiently hydroxylate steroid precursors and thereby provides the placenta with those hydroxylated steroids necessary for estrogen production. The placenta has almost no 17α-hydroxylase or 17,20 desmolase activity. For this reason, the precursors of the estrogens produced by the placenta must be supplied by the fetal or maternal systems. The placenta exhibits a robust ability to cleave sulfate groups from steroids. Placental sulfatase is integral to the formation of estrogens from fetal sulfated precursors. As the placenta lacks 17-α hydroxylase, all estriol produced during pregnancy arises from 17-α hydroxylated fetal precursors.
Progesterone
The corpus luteum of the ovary supplies progesterone until about 10 weeks’ gestation. This supports pregnancy until placental progesterone production takes over in weeks 7–9 of gestation. The levels of 17α-hydroxyprogesterone produced by the corpus luteum rise in early pregnancy but fall by 10 weeks’ gestation. After that time, placental production of progesterone dominates the maternal system and the placenta exhibits almost no 17α-hydroxylase activity.
Unlike other steroid-producing glands, the placenta lacks the enzymes to form cholesterol from acetate; therefore, progesterone produced by the syncytiotrophoblast is dependent on maternal cholesterol. hCG produced by the placenta supports the synthesis and secretion of progesterone within the placenta. Estrogens may also promote progesterone production by stimulating cholesterol uptake by the placenta and placental enzymatic conversion of cholesterol to pregnenolone. As a result, very large amounts of progesterone are produced and secreted by the placenta into the maternal bloodstream. This progesterone is active locally within the uterus, where it maintains the decidual lining of the uterus and relaxes the smooth muscle cells of the myometrium. It also has peripheral effects upon vascular smooth muscle and other organs that must adapt to the demands of pregnancy (Chapters 20 and 21).
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
