Chorionic Gonadotropin (hCG) Fragments

Definition
Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced during pregnancy1. It is made by the developing embryo soon after conception1. Its role is to prevent the disintegration of the corpus luteum of the ovary and thereby maintain progesterone production that is critical for a pregnancy in humans1.

Discovery
The activity of hCG was first identified in 1927 when it was demonstrated that the blood and urine of pregnant women contained a gonad-stimulating substance that could induce follicular maturation in immature female mice2.

Classification
hCG is a member of glycoprotein hormone family that also includes LH, FSH and TSH3.

Structural Characteristics
hCG is a heterodimer of two subunits - a and b4. a-subunit consists of 92 amino acids and two carbohydrate moieties that are linked to Asn52 and Asn784. The b?-subunit is 145 amino acids long with six carbohydrate moieties attached to Asn13 and Asn304. It is more acidic that the a- subunit4.

Mode of action
hCG acts through the LHCG receptor that upon binding of hCG activates the G protein that is bound to the receptor internally that in turn activates cAMP3. cAMP activates the cAMP-dependent protein kinase that in turn triggers the transcription of several target genes in the nucleus3.

Functions
hCG promotes the maintenance of the corpus luteum during the beginning of pregnancy, causing it to secrete the hormone progesterone that enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus3. Due to its highly-negative charge, hCG may repel the immune cells of the mother, protecting the fetus during the first trimester. It has also been hypothesized that hCG may be a placental link for the development of local maternal immunotolerance5. Because of its similarity to LH, hCG can also be used clinically to induce ovulation in the ovaries as well as testosterone production in the testes3. It also plays a role in cellular differentiation/proliferation and may activate apoptosis6. hCG levels are used as a measure during pregnancy testing3. Human chorionic gonadotropin is extensively used as a parenteral fertility medication3.

References
1.de Medeiros SF, Norman RJ (2009). Human choriogonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights. Hum Reprod Update, 15(1):69-95.
2.Ascheim S and Zondek B (1927). Das Hormon des Hypophysenvorderlappens: testobjekt zum nachweis des hormons. Klin Wochenschr 6,248–252.
3.Stenman UH, Tiitinen A, Alfthan H, Valmu L (2006) The classification, functions and clinical use of different isoforms of HCG. Hum Reprod Update, 12(6):769-84.
4.Albertini A, Ghielmi S and Belloli S (1982). Structure, immunochemical properties and immunoassay of human chorionic gonadotropin. Intl. J. Clin. & Lab. Res., 12(1), 289-298.
5.Kayisli U, Selam B, Guzeloglu-Kayisli O, Demir R, Arici A (2003). Human chorionic gonadotropin contributes to maternal immunotolerance and endometrial apoptosis by regulating Fas-Fas ligand system. J. Immunol., 171 (5), 2305–13.
6.Michels KB, Xue F, Colditz GA, Willett WC (2007). Induced and spontaneous abortion and incidence of breast cancer among young women: a prospective cohort study. Arch. Intern. Med., 167 (8): 814–20.