Clinical Pathology: General Principles, Lab Management, Clinical Chemistry

• Intact human chorionic gonadotropin (hCG) is a glycoprotein consisting of a 92–amino acid α-subunit and a 145–amino acid β-subunit with a molecular weight of about 37.9 kDa. The β-subunit determines the biologic activity of hCG. The α-subunit of hCG has the same amino acid sequence as in thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The β-subunit of hCG has a slightly different amino acid sequence compared with the β-subunits of TSH, LH, and FSH; this differentiates hCG from these other glycoprotein hormones.

• Hyperglycosylated hCG is a glycosylated variant of hCG. Hyperglycosylated hCG consists of 42% carbohydrate by molecular weight compared with 30% in intact hCG. Hyperglycosylated hCG is the major hCG molecule that is produced between 3 to 5 weeks of pregnancy and accounts for about 87% of the total hCG in the third week of pregnancy.

• Intact hCG accounts for most of the remaining hCG at 3 weeks of pregnancy. The amount of hyperglycosylated hCG rapidly decreases after 3 weeks, and at 6 weeks intact hCG is the predominant form of circulating hCG. The amount of hyperglycosylated hCG in the second and third trimesters is less than 1% of total hCG.

• Intact hCG promotes progesterone production during the first 3 weeks of pregnancy. Hyperglycosylated hCG stimulates implantation and the growth of placenta. Intact hCG and hyperglycosylated hCG together are believed to be responsible for implantation of the embryo in early pregnancy.

• Hyperglycosylated hCG is also the major form of hCG in choriocarcinoma. Nicked hCG is formed from the β-subunit of hCG, usually by enzymatic cleavage of the peptide bonds at positions 47 to 48. Nicking inactivates hCG. Nicked hCG may be present in serum after removal of a hydatidiform mole or in postgestational choriocarcinoma. Free β-hCG levels are used in the first trimester as part of a screening protocol for Down syndrome. Free β-hCG levels in serum are a sensitive marker for testicular cancer.

Cole LA: Biological functions of HCG and HCG-related molecules. Reprod Biol Endocrinol 2010;8(102):1–14.

Lempiainen A, Stenman UH, Blomqvist C, et al: Free β-subunit of human chorionic gonadotropin in serum in a diagnostically sensitive marker of seminomatous testicular cancer. Clin Chem 2008;54(11):1840–1843.

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