During the first 2 to 4 weeks of pregnancy, rising hCG levels maintain production of estradiol in the maternal corpus luteum. Production of both progesterone and estrogens in the maternal ovaries drops signiicantly by the 7th week of pregnancy. At this time, there is a luteal-placental transition. By the 7th week, more than half of estrogen entering maternal circulation is produced in the placenta (MacDonald, 1965a; Siiteri, 1963,i1966). Subsequently, the placenta produces a continually increasing magnitude of estrogen. Near term, normal human pregnancy is a hyperestrogenic state, and syncytiotrophoblast is producing estrogen in amounts equivalent to that produced in 1 day by the ovaries of no fewer than 1000 ovulatory women. This hyperestrogenic state terminates abruptly after delivery of the placenta.
In human trophoblast, neither cholesterol nor, in turn, proges :e�8!e :�� �e�.'e !s F"�C�!!S0!" For �'tr0g�n hi)"ynth�."is. Thi� is because steroid 17a-hydroxylasel1,20-yase (CP17Al) is not expressed in the human placenta. This essential enzyme converts 17-0H progesterone (a C2I steroid) to androstenedione, which is a C'9 steroid and an estrogen precursor. Consequently, the conversion of C2I steroids to C'9 steroids is not possible.
However, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) are also C'9 steroids and are produced by maternal and fetal adrenal glands. These two steroids can serve as estrogen precursors (Fig. 5-20). Ryan (1959a) found that the placenta had an exceptionally high capacity to convert appropriate C'9 steroids to estrone and estradiol. The conversion of DHEA-S to estradiol requires placental expression of four key enzymes
FIGURE 5-20 Schematic presentation of estrogen biosynthesis in the human placenta. Dehydroepiandrosterone sulfate (DHEAS), secreted in prodigious amounts by the fetal adrenal glands, is converted to 16a-hydroxydehydroepiandrosterone sulfate (16aOHDHEAS) in the fetal liver. These steroids, DHEAS and 16aOHDHEAS, are converted in the placenta to estrogens, that is, 17�-estradiol (E) and estriol (E3). Near term, half of E2 is derived from fetal adrenal DHEAS and half from maternal DHEAS. On the other hand, 90 percent of E3 in the placenta arises from fetal 16aOHDHEAS and only 10 percent from all other sources.
that are located principally in syncytiotrophoblast (Bonenfant, 2000; Salido, 1990). First, the placenta expresses high levels of steroid sulfatase (STS), which converts the conjugated DHEAS to DHEA. DHEA is then acted upon by 33-hydroxysteroid dehydrogenase type 1 (33HSD) to produce androstenedione. Cytochrome P450 aromatase (CYP19) then converts androstenedione to estrone, which is then converted to estradiol by 173-hydroxysteroid dehydrogenase type 1 (173HSDl).