Synthesis of the .-and 3-chains of hCG is regulated separately. A single gene located on chromosome 6 encodes the a-subunit. Seven genes on chromosome 19 encode for the �-hCG-3-LH family of subunits. Six genes code for 3-hCG and one for 3-LH (Miller-Lindholm, 1997). Both subunits are synthesized as larger precursors, which are then cleaved by endopeptidases. Intact hCG is then assembled and rapidly released by secretory granule exocytosis (Morrish, 1987). There are multiple forms of hCG in maternal plasma and urine that vary enormously in bioactivity and immunoreactivity. Some result from enzymatic degradation, and others from modifications during molecular synthesis and processing.
Before 5 weeks, hCG is expressed both in the syncytiotrophoblast and in cytotrophoblasts (Mamo, 1992). Later, in the irst trimester when maternal serum levels peak, hCG is produced almost solely in the syncytiotrophoblast (Beck, 1986; Kurman, 1984). At this time, mRNA concentrations of both .-and 3-subunits in the syncytiotrophoblast are greater than at term (Hoshina, 1982). This may be an important consideration when hCG is used as a screening procedure to identiy abnormal fetuses.
Circulating free levels of 3-subunit are low to undetectable throughout pregnancy. In part, this is the result of its rate-limiting synthesis. Free a-subunits that do not combine with the 3-subunit are found in placental tissue and maternal plasma. Levels of the a-subunit rise gradually and steadily until they plateau at approximately 36 weeks' gestation. At this time, they account for 30 to 50 percent of hormone (Cole, 1997). Thus, .-hCG secretion roughly corresponds to placental mass, whereas secretion of complete hCG molecules is maximal at 8 to 10 weeks.
TABLE 5-2. Protein Hormones Produced by the Human Placenta
Primary Non-placental Shares Structural or Hormone Site of Expression Function Similarity Functions
LH, FSH,lTSH
GH, prolactin
The combined hCG molecule is detectable in plasma of pregnant women 7 to 9 days after the midcycle surge of LH that precedes ovulation. hus, hCG likely enters maternal blood at the time of blastocyst implantation. Plasma levels rise rapidly, doubling every 2 days in the first trimester (Fig. 5-18). Appreciable fluctuations in levels for a given patient are observed on the same day.
Intact hCG circulates as multiple highly related isoforms with variable cross-reactivity between commercial assays. hus, calculated serum hCG levels can vary considerably among the more than a hundred available assays. his emphasizes the need to use the same assay type when clinically measuring serial hCG levels. Peak maternal plasma levels reach approximately 50,000 to 100,000 mIU/mL between the 60th and 80th days after menses. At 10 to 12 weeks' gestation, plasma levels begin to decline, and a nadir is reached by approximately 16 weeks. Plasma levels are maintained at this lower level for the remainder of pregnancy.
The pattern of hCG appearance in fetal blood is similar to that in the mother. Fetal plasma levels, however, are only about 3 percent of those in maternal plasma. Amnionic fluid hCG concentration early in pregnancy is similar to that in maternal plasma. As pregnancy progresses, hCG concentration in
Aids maternal adaptation to fetal energy requirements
Relaxes smooth-muscle; initiates parturition? Promotes fetal and maternal glucocorticoid production Regulates trophoblast hCG production