Structure: Human chorionic gonadotropin is a glycoprotein composed
of 244 amino acids with a molecular mass of 36.7 kDa.
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 α (alpha) subunit is 92 amino acids long. The sequence of the
alpha unit can be found on UniProtKB with ID: P01215[25-116].
The β-subunit of hCG gonadotropin contains 145 amino acids, encoded
by six highly homologous genes that are arranged in tandem and
inverted pairs on chromosome 19q13.3 - CGB (1, 2, 3, 5, 7, 8). The
sequence of the beta unit can be found on UniProtKB with ID:
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.
FunctionHuman 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. It has also been suggested that hCG levels
are linked to the severity of morning sickness in pregnant women.
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
pregnant women to extract hCG for use in fertility treatment.
Human chorionic gonadotropin also plays a role in cellular
differentiation/proliferation and may activate apoptosis.
ProductionLike other gonadotropins, hCG can be extracted from urine
or by genetic modification. Pregnyl, Follutein, Profasi, Choragon
and Novarel use the former method, derived from the urine of
pregnant women. Ovidrel, on the other hand, is a product of
recombinant DNA. hCG is produced from the syncytiotrophoblast cell
HCG formsTotal hCG, C-terminal peptide total hCG, intact hCG, free
ß-subunit hCG, ß-core fragment hCG, hyperglycosylated hCG, nicked
hCG, alpha hCG, pituitary hCG.
MethodolgyhCG immunoassays are based on the sandwich principal and
labeled with an enzyme, dye, or chemilluminescence. Pregnancy urine
dipstick principle based on lateral flow technique.
Testing Levels of hCG may be measured in the blood or urine. Most
commonly, this is done as a pregnancy test, intended to indicate
the presence or absence of an implanted embryo. Testing for hCG may
also be done when diagnosing or monitoring germ cell tumors and
gestational trophoblastic disease.
Concentrations are commonly reported in thousandth international
units per milliliter (mIU/ml). The international unit of hCG was
originally established in 1938 and has been redefined in 1964 and
in 1980. At the present time, 1 international unit is equal to
approximately 2.35×10-12 moles, or about 6×10-8 grams.
Most tests employ a monoclonal antibody, which is specific to the
β-subunit of hCG (β-hCG). This procedure is employed to ensure 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,
whereas the presence of hCG almost always indicates pregnancy.)
The urine test may be a chromatographic immunoassay or any of
several other test formats, home-, physician's office-, or
laboratory-based. Published detection thresholds range from 20
to 100 mIU/ml, depending on the brand of test. Early in pregnancy,
more accurate results may be obtained by using the first urine of
the morning (when hCG levels are highest). When the urine is dilute
(specific gravity less than 1.015), the hCG concentration may not
be representative of the blood concentration, and the test may be
The serum test, using 2-4 mL of venous blood, is typically a
chemiluminescent or fluorimetric immunoassay that can detect βhCG
levels as low as 5 mIU/ml and allows quantification of the βhCG
concentration. The ability to quantitate the βhCG level is useful
in the monitoring germ cell and trophoblastic tumors, followup care
after miscarriage, and in diagnosis of and follow-up care after
treatment of ectopic pregnancy. The lack of a visible fetus on
vaginal ultrasound after the βhCG levels have reached 150,000
mIU/ml is strongly indicative of an ectopic pregnancy.
As pregnancy tests, quantitative blood tests and the most sensitive
urine tests usually detect hCG between 6 to 12 days after
ovulation. However, it must be taken into account that total hCG
levels may vary in a very wide range within the first 4 weeks of
gestation, leading to false results during this period of time.
Gestational trophoblastic disease like Hydatidiform moles ("molar
pregnancy") or Choriocarcinoma may produce high levels of βhCG (due
to the presence of syncytialtrophoblasts- part of the villi that
make up the placenta) despite the absence of an embryo. This, as
well as several other conditions, can lead to elevated hCG readings
in the absence of pregnancy.
hCG levels are also a component of the triple test, a screening
test for certain fetal chromosomal abnormalities/birth defects.
Reference levelsThe following is a list of serum hCG levels. (LMP
is the last menstrual period dated from the first day of your last
period.) The levels grow exponentially after conception and
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