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Information about Human Chorionic Gonadotropin

HCG polypeptide structure
chorionic gonadotropin, beta polypeptide
Identifiers
SymbolCGB
Entrez1082
HUGO1886
OMIM118860
PDB1HCN
RefSeqNM_000737
UniProtP01233
Other data
LocusChr. 19 q13.3
Human chorionic gonadotropin (hCG) is a peptide hormone produced in pregnancy, that is made by the embryo soon after conception and later by the syncytiotrophoblast (part of the placenta). 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 humans. hCG may have additional functions, for instance it is thought that it affects the immune tolerance of the pregnancy. Early pregnancy testing generally is based on the detection or measurement of hCG. Because hCG is produced also by some kinds of tumor, hCG is an important tumor marker, but it is not known whether this production is a contributing cause or an effect of tumorigenesis.

Structure

hCG is an oligosaccharide glycoprotein composed of 244 amino acids with a molecular mass of 36.7 kDa. Its total dimensions are 75x35x30 angstroms (7.5x3.5x3 nanometers).

It is heterodimeric, with an α (alpha) subunit identical to that of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH) and β (beta) subunit that is unique to hCG.
  • The α (alpha) subunit is 92 amino acids long and has dimensions 60x25x15 angstroms (6x2.5x1.5 nm).
  • βhCG is encoded by six highly homologous genes which are arranged in tandem 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

hCG 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.

Pregnancy testing

Pregnancy tests measure the levels of hCG in the blood or urine to indicate the presence or absence of an implanted embryo.

In particular, most pregnancy tests employ a monoclonal antibody (MAb), which is specific to the β-subunit of hCG (βhCG). This is important so that tests do not make false positives by confusing hCG with LH and FSH. (The latter two are always present at varying levels in the body, while hCG levels are negligible except during pregnancy.)
  • The urine test may be a chromatographic immunoassay or any of several other test formats, home-, physician's office-, or laboratory-based.[3] Published detection thresholds range from 20 to 100 mIU/ml (milli International Units per milli-liter), depending on the brand of test.[4] The urine should be the first urine of the morning when hCG levels are highest. If the specific gravity of the urine is above 1.015, the urine should be diluted.
  • The serum test, using 2-4 mL of venous blood, is typically a chemiluminescent or fluorimetric immunoassay<ref name="henry" /> that can detect βhCG levels as low as 5 mIU/ml and allows quantitation of the βhCG concentration. The ability to quantitate the βhCG level is useful in the evaluation of ectopic pregnancy and in monitoring germ cell and trophoblastic tumors.
Hydatidiform moles ("molar pregnancy") may produce high levels of βhCG, despite the absence of an embryo. This, as well as several other conditions, can lead to false positive readings of pregnancy tests.

Tumor marker

β-hCG is also secreted by some cancers including choriocarcinoma, teratoma with elements of choriocarcinoma (this is rare), and islet cell tumor.

Main article: tumor marker

Use as medication

hCG 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 who undergo IVF, typically 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 this is due to the high concentration of hCG, and that the beta-subunit of this protein is active against HIV-1.[5]

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. Novarel and hCG from APP are typically considered generics in the United States.

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 HPTA (hypothalamic-pituitary-testicular axis). 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 / 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

1. ^ 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. 
2. ^ 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. 
3. ^ 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. 
4. ^ Waddell, Rebecca Smith (2006). FertilityPlus.org. Home Pregnancy Test hCG Levels and FAQ. Retrieved on 2006-06-17.
5. ^ (2006). "Can Lysozyme be used as an anti-HIV drug?". Lysozyme.co.uk. Retrieved on 2007-10-11.

External links

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Endocrine system: hormones/endocrine glands (Peptide hormones, Steroid hormones)
Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α (FSH, LH, TSH), GH, prolactin, POMC (ACTH, MSH, endorphins, lipotropin)
Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA
Thyroid axis Thyroid: thyroid hormone (T3 and T4) - calcitonin - Parathyroid: PTH
Gonadal axisTestis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin (pregnancy)
Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin
Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Liver/other: Insulin-like growth factor (IGF-1, IGF-2)
Target-derivedNGF, BDNF, NT-3
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Hugo is a male given name, a latinized form of the name Hugh, a German/Teutonic name meaning "Bright in Mind and Spirit".

Hugo is one of the most popular names in Europe ranking as high as #2 in France, #6 in Spain, and #7 in Belgium in 2006.
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Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.

Like other proteins, peptide hormones are synthesized from amino acids according to an mRNA template, which is itself synthesized from a DNA
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Pregnancy is the carrying of one or more offspring, known as a fetus or embryo, inside the body of a female mammal such as a human. In a pregnancy, there can be multiple gestations (for example, in the case of twins or triplets).
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Fertilization (also known as conception, fecundation and syngamy), is fusion of gametes to form a new organism of the same species. In animals, the process involves a sperm fusing with an ovum, which eventually leads to the development of an embryo.
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Syncytiotrophoblasts are multinucleated cells found in the placenta of human embryos.

They are the outer syncytial layer of the trophoblasts and actively invade the uterine wall.
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The placenta is an ephemeral (temporary) organ present in placental vertebrates, such as some mammals and sharks during gestation (pregnancy).

The placenta develops from the same sperm and egg cells that form the fetus, and functions as a fetomaternal organ with two
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The corpus luteum (Latin for "yellow body") (plural corpora lutea) is a temporary endocrine structure in mammals, involved in the production of the progestogens which are needed for the maintenance of a pregnancy.
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For ovary as part of plants see ovary (plants)
An ovary is an egg-producing reproductive organ found in female organisms. They are usually purple. It is often found in pairs as part of the vertebrate female reproductive system.
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Progesterone is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species. Progesterone belongs to a class of hormones called progestogens, and is the major naturally occurring human
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Pregnancy is the carrying of one or more offspring, known as a fetus or embryo, inside the body of a female mammal such as a human. In a pregnancy, there can be multiple gestations (for example, in the case of twins or triplets).
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A pregnancy test is a test to determine whether or not a woman is pregnant.

Modern tests

The earliest test for pregnancy is a rosette inhibition assay for early pregnancy factor (EPF). EPF can be detected in blood within 48 hours of fertilization.
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Tumor or tumour (via Old French tumour from Latin tumor "swelling") is an abnormal growth or mass of tissue. A tumor can be either malignant or benign.
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Tumor markers are substances found in the blood, urine or body tissues that can be elevated in cancer. There are many different tumor markers. They are used in oncology to help determine the presence of cancer.
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Tumorigenesis is the formation of tumors in the body, often caused by oncogenes. These tumors are the result of uncontrollable reproduction (cell division) due to alterations in the cell's genetic code, creating lesions in the tissue where they reside.
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An oligosaccharide is a saccharide polymer containing a small number (typically three to ten[1]) of component sugars, also known as simple sugars.

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amino acid is a molecule that contains both amine and carboxyl functional groups. In biochemistry, this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent.
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molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12).
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Possible meanings:
  1. Kachin Defense Army
  2. Kentucky Distillers Association
  3. Kongsberg Defence & Aerospace
  4. kDa Atomic mass unit
  5. Kotelawala Defence Academy

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1 nanometre =
SI units
010−9 m 010−3 μm
US customary / Imperial units
010−9 ft 010−9 in
A nanometre (American spelling: nanometer, symbol nm
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dimer refers to a molecule composed of two identical subunits or monomers linked together.

Chemistry

The molecules in a dimer are connected by covalent bonds or weaker interactions such as hydrogen bonds.
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In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles (or "coassembles") with other protein molecules to form a multimeric or oligomeric protein.
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Luteinizing hormone (LH, also known as lutropin[1]) is a hormone synthesized and secreted by gonadotropes in the anterior lobe of the pituitary gland.
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For other uses of the term FSH, see .


Follicle stimulating hormone (FSH) is a hormone synthesised and secreted by gonadotropes in the anterior pituitary gland.
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