Native Human Chorionic Gonadotropin α (HCGα)

hCG is made by placental syncytiotrophoblast cells, which stimulates the embryo growth and keeps it fertile. In the first half of pregnancy, hCG increases the release of progesterone, estradiol and estrone by turning the postovulatory ovary into a gestational corpus luteum. And hCG binds to its receptor in order to perform other things, such as induce uterine endothelium angiogenesis, soothe the myometrium of the uterus, and activate immune response. hCG promotes immunomodulation by altering dendritic cell activity, decreasing T cell activation and cytokine production, promoting Treg cell recruitment, and increasing proliferation of uterine NK cells at the maternal-fetal interface.

hCG belongs to the glycoprotein hormone group. These hormones do very different biological things but have very similar structure, consisting of an alpha and beta subunit. Alpha subunit is almost the same in every member of this family, within one species and across mammals, while beta subunit differs and makes each hormone different in its biological activity. The hCG molecule is formed by the non-covalent binding of its alpha and beta subunits. The hCG alpha subunit is homologous to LH and TSH, so there's some immune cross-reactivity. Alpha is encoding by the gene CGA, and beta by six non-allelic genes (CGB1, CGB2, CGB3, CGB5, CGB7, and CGB8). These genes are thought to have evolved through duplication of the LHB gene, resulting in a high degree of nucleotide sequence conservation (85–99% similarity).

Figure 1. Location and organization of CGA gene and LH-CGB cluster of genes
(Source: Fournier T, et al. 2015)

The hCG-β exhibits strong antigen specificity and has significant research value in areas such as pregnancy diagnosis and infertility treatment. While the α-subunit of hCG alone lacks biological activity, it plays a crucial role in forming the complete hCG molecule. Researchers have observed not only that the α-subunit is involved in signal transduction and also has effects on the activity of hCG-β, but that it is overexpressed in pathological conditions. They are non-cystic tumours (brain, lung, colon, breast) and atypical pregnancies (ectopic pregnancy, preeclampsia). What's more, hCG has a strong relationship with tumour differentiation, invasion and dissemination. hCG that non-trophoblastic tumors release is known as ectopic hCG. Some researchers suggest that the hCG-α subunit holds potential diagnostic and therapeutic value. Its antagonists may have the ability to inhibit the development and progression of such tumors and abnormal pregnancies.

Native HCGα