The establishment and maintenance of a pregnancy is dependent on progesterone and during the first 6–7 weeks this is produced by the corpus luteum. In humans, the continued production of progesterone by the corpus luteum depends on chorionic gonadotrophin, hCG, secreted by the trophoblast cells of the embryo within one day of the beginning of implantation. This is 9–11 days following the midcycle LH peak and 8 days following ovulation. If the embryo is unable to secrete sufficient amounts of hCG during this crucial time, the corpus luteum will undergo regression, progesterone production will cease, and the pregnancy will fail. The dependency of the pregnancy on progesterone from the corpus luteum lasts for the first 6–7 weeks of the pregnancy when the placenta takes over progesterone production in the luteal-placental shift.
Human chorionic gonadotropin is a heterodimeric glycoprotein of 57 kDa. Its 92-amino acid α subunit is identical in amino acid sequence to those of human LH, FSH, and TSH. The β subunit of hCG is very similar to that of LH (80% homology for the first 115 amino acids) except that the carboxy terminus of hCG has an extra 22 amino acids. Noncovalent hydro phobic bonding holds the two subunits together. The single gene for the α subunit is located on chromosome 6 and is expressed in both the cytotrophoblast and the syncytiotrophoblast. A cluster of six genes on chromo some 19 encode the hCG β subunit, three of which are expressed in the syncytiotrophoblast, which also carries out the glycosylation of both subunits as well as the assembly and secretion of the mature dimeric hormone. LH and hCG share the same receptor, encoded by the single copy LHCGR gene on chromosome 2.
The regulation of hCG synthesis and secretion by the trophoblast are not clearly understood. Many placental molecules, including GnRH, activin, and inhibin, have been implicated, but a clear picture has not yet emerged of the integrated actions of these and other hormones on hCG production.
The levels of hCG rise exponentially for about the first 8 weeks of pregnancy (Figure1), doubling approximately every 72 hours if there is a single fetus and more rapidly if there are two or more viable embryos. Levels then fall off, as the fetoplacental unit takes over in the production of progesterone. Several functions for hCG, in addition to maintenance of progesterone production by the corpus luteum, have been postulated. One for which there is considerable evidence is its role in the stimulation of the fetal testis to secrete testosterone early in development prior to the ability of the fetal pituitary to secrete sufficient amounts of LH for this function.
Fig1. Chorionic gonadotrophin and placental lactogen levels during pregnancy. The graph shows the levels of human chorionic gonadotrophin (hCG) and placental lactogen (hPL) throughout pregnancy. hPL is also known as chorionic somatomammotrophin, CS or hCS. hCG is detectable a few days following fertilization, rises exponentially to a peak at about 8 weeks, then declines to a plateau for the remainder of the pregnancy. hPL is first detectable at about 5 weeks and continues to rise until term.
Immunoassays can detect the β subunit of hCG in blood at the level of 1mIU/mL and a 10.5 kDa core fragment of the β subunit in urine at a level 10–100 mIU/mL. This level of sensitivity is sufficient to detect a pregnancy with a blood sample (5 mIU or greater) within a day of implantation and within the next 2–4 days using urine, as in home pregnancy tests.
