Abstract
Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG.For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis.While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy.New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic disease, diagnosing placental site trophoblastic tumor, managing testicular germ cell malignancies, and monitoring other human malignancies. There are very few molecules with such wide and varying functions as regular hCG and its variants, and very few tests with such a wide spectrum of clinical applications as total hCG.
Highlights
In 1920 Hirose showed a hormonal link between a human placental hormone and progesterone production by corpus luteal cells [1]
The 1980s and 1990s saw the determination of the structures of the N- and O-linked oligosaccharides on human chorionic gonadotropin (hCG) as produced in pregnancy and gestational trophoblastic diseases (Figure 2) [18,19], it saw the elaboration of the hCG subunit gene structures [20], and to our understanding of the hCG/luteinizing hormone (LH) receptor and the mechanisms of hCG endocrinology whereby hCG promotes progesterone production [21,22]
It has moved from hCG a hormone produced by trophoblast cells that promotes progesterone production by luteal cells to hCG as group of molecules each with different functions
Summary
In 1920 Hirose showed a hormonal link between a human placental hormone and progesterone production by corpus luteal cells [1]. The 1980s and 1990s saw the determination of the structures of the N- and O-linked oligosaccharides on hCG as produced in pregnancy and gestational trophoblastic diseases (Figure 2) [18,19], it saw the elaboration of the hCG subunit gene structures [20], and to our understanding of the hCG/LH receptor and the mechanisms of hCG endocrinology whereby hCG promotes progesterone production [21,22] Was this the completion of the hCG physiology, biochemistry and immunoassay story? There has been the discovery of numerous new applications when measuring only hyperglycosylated hCG and only the hyperglycosylated and regular free β-subunit This review examines these hCG variant molecules and how the past 10 years they have changed the way they are viewed. General Pregnancy (6 weeks – term) Biochemical pregnancy Spontaneous abortion Ectopic pregnancy
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