Structure
Human chorionic gonadotropin is an oligosaccharide([生化]低聚糖,寡糖) glycoprotein([化]糖蛋白类, 醣蛋白) composed of 244 amino acids with a molecular mass of 36.7 kDa. Its total dimensions are 75×35×30 angstroms (7.5×3.5×3 nanometers(十亿分之一公尺,毫微米)).
It is heterodimeric, with an α (alpha) subunit identical to that of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and β (beta) subunit that is unique to hCG.
- The beta subunit of human chorionic gonadotropin is encoded by six highly-homologous genes that are arranged in tandem(一前一后) and inverted pairs on chromosome 19q13.3 - CGB (1, 2, 3, 5, 7, 8).
The two subunits create a small hydrophobic core surrounded by a high surface area-to-volume ratio: 2.8 times that of a sphere. The vast majority of the outer amino acids are hydrophilic.
Function
Human chorionic gonadotropin interacts with the LHCG receptor and promotes the maintenance of the corpus luteum during the beginning of pregnancy, causing it to secrete the hormone progesterone. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus. 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 immunotolerance. For example, hCG-treated endometrial cells induce an increase in T cell apoptosis (dissolution of T-cells). These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance, and may facilitate the trophoblast invasion, which is known to expedite fetal development in the endometrium.[1] It has also been suggested that hCG levels are linked to the severity of morning sickness in pregnant women.[2]
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 testes. As the most abundant biological source is women who are presently pregnant, some organizations collect urine from gravidae to extract hCG for use in fertility treatment.
Human chorionic gonadotropin also plays a role in cellular differentiation/proliferation and may activate apoptosis.[3]
Tumor marker
The β subunit of human chorionic gonadotropin is secreted also by some cancers including choriocarcinoma, germ cell tumors, teratoma with elements of choriocarcinoma (this is rare), and islet cell tumor. For this reason a positive result in males can be a test for cancer.
Use as medication
Human chorionic gonadotropin is extensively used as a parenteral fertility medication in lieu of luteinizing hormone. In the presence of one or more mature ovarian follicles, ovulation can be triggered by the administration of hCG. As ovulation will happen about 40-45 hours after the injection of hCG, procedures can be scheduled to take advantage of this time sequence. Thus, patients that undergo IVF, in general, receive hCG to trigger the ovulation process, but have their eggs retrieved at about 36 hours after injection, a few hours before the eggs actually would be released from the ovary.
As hCG supports the corpus luteum, administration of hCG is used in certain circumstances to enhance the production of progesterone.
In the male, hCG injections are used to stimulate the leydig cells to synthesize testosterone. The intratesticular testosterone is necessary for spermatogenesis from the sertoli cells. Typical uses for hCG in men include hypogonadism and fertility treatment.
During first few months of pregnancy, the transmission of HIV-1 from woman to fetus is extremely rare. It has been suggested that this is due to the high concentration of hCG, and that the beta-subunit of this protein is active against HIV-1.[6]
Production
Like other gonadotropins, hCG can be extracted from urine or by genetic modification. Pregnyl, Follutein, Profasi, and Novarel use the former method, derived from the urine of pregnant women. Ovidrel, on the other hand, is a product of recombinant DNA.
Use with anabolic steroids
In the world of performance enhancing drugs, hCG is increasingly used in combination with various anabolic androgenic steroid (AAS) cycles.
When AAS are put into a male body, the body's natural negative-feedback loops cause the body to shut down its own production of testosterone via shutdown of the hypothalamic-pituitary-testicular axis (HPTA). High levels of AASs that mimic the body's natural testosterone trigger the hypothalamus to shut down its production of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Without GnRH, the pituitary gland stops releasing luteinizing hormone (LH). LH normally travels from the pituitary via the blood stream to the testes, where it triggers the production and release of testosterone. Without LH, the testes shut down their production of testosterone, causing testicular atrophy.
In males, hCG mimics LH and helps restore and maintain testosterone production in the testes. As such, hCG is commonly used during and after steroid cycles to maintain and restore testicular size as well as endogenous testosterone production. However, if hCG is used for too long and in too high a dose, the resulting rise in natural testosterone will eventually inhibit its own production via negative feedback on the hypothalamus and pituitary.
References
- ^ 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. PMID 12928375.
- ^ Askling, J; Erlandsson G, Kaijser M, et al. (1999 Dec 11). "Sickness in pregnancy and sex of child". The Lancet 354 (9195): 2053. PMID 10636378. Retrieved on 2006-07-13.
- ^ 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. doi:10.1001/archinte.167.8.814. PMID 17452545.
- ^ a b Richard A. McPherson, Matthew R. Pincus, (2006). Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st edition, Philadelphia: Saunders. ISBN 1-4160-0287-1.
- ^ Waddell, Rebecca Smith (2006). FertilityPlus.org. Home Pregnancy Test hCG Levels and FAQ. Retrieved on 2006-06-17.
- ^ (2006). "Can Lysozyme be used as an anti-HIV drug?". Lysozyme.co.uk. Retrieved on 2007-10-11.
