Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene. The AFP gene is
located on the q arm of chromosome 4. AFP is a major plasma protein produced by
the yolk sac and the liver during fetal development. It is thought to be the fetal form of serum
albumin. AFP binds to copper, nickel, fatty acids and bilirubin and is found in monomeric,
dimeric and trimeric forms.
Structure AFP is a glycoprotein of 591 amino acids and
a carbohydrate moiety. Function
AFP is the most abundant plasma protein found in the human fetus. Plasma levels decrease
rapidly after birth but begin decreasing prenatally starting at the end of the first trimester.
Normal adult levels are usually achieved by the age of 8 to 12 months. The function of
AFP in adult humans is unknown; however, in rodents it binds estradiol to prevent the
transport of this hormone across the placenta to the fetus. The main function of this is
to prevent the virilization of female fetuses. As human AFP does not bind estrogen, its function
in humans is less clear. The rodent AFP system can be overridden with
massive injections of estrogen, which overwhelm the AFP system and will masculinize the fetus.
The masculinizing effect of estrogens may seem counter-intuitive since estrogens are
critical for the proper development of female secondary characteristics during puberty.
However, this is not the case prenatally. Gonadal hormones from the testes, such as
testosterone and antimullerian hormone are required to cause development of a phenotypic
male. Without these hormones the fetus will develop into a phenotypic female even if genetically
XY. Interestingly, the conversion of testosterone into estradiol by aromatase in many tissues
may be an important step in masculinization of that tissue. Masculinization of the brain
is thought to occur both by conversion of testosterone into estradiol by aromatase,
but also by de novo synthesis of estrogens within the brain. Thus, AFP may protect the
fetus from maternal estradiol that would otherwise have a masculinizing effect on the fetus,
but its exact role is still controversial. Serum levels
Maternal In pregnant women, fetal AFP levels can be
monitored in urine. AFP is cleared strongly from the kidneys allowing AFP to tend to mirror
fetal serum levels. In contrast, maternal serum AFP levels are much lower but continue
to rise until about week 32. This is thought to be because the mother is not utilising
the AFP, and therefore clears it from her system without issue.
Infants The normal range of AFP for adults and children
is variously reported as under 50, under 10, and under 5 ng/mL. At birth, normal infants
have AFP levels 4 or more orders of magnitude above this normal range, that decreases to
a normal range over the first year of life. During this time, the normal range of AFP
levels spans approximately 2 orders of magnitude. Correct evaluation of abnormal AFP levels
in infants must take into account these normal patterns.
Very high AFP levels may be subject to hooking, which results in the level being reported
significantly lower than the actual concentration. This is important for analysis of a series
of AFP tumor marker tests, e.g. in the context of post-treatment early surveillance of cancer
survivors, where the rate of decrease of AFP has diagnostic value.
Clinical significance
AFP is measured in pregnant women through the analysis of maternal blood or amniotic
fluid, as a screening test for a subset of developmental abnormalities. Some of the diseases
in which AFP will be elevated in a person are listed below:
Omphalocele Hepatocellular carcinoma/hepatoma: ↑ α-fetoprotein
Neural tube defects: ↑ α-fetoprotein in amniotic fluid and maternal serum
Nonseminomatous germ cell tumors Yolk sac tumor
Ataxia telangiectasia: Elevation of AFP is used as one factor in the diagnosis of ataxia
telangiectasia. Tumors: AFP can also be used as a biomarker
to detect a subset of tumors in non-pregnant women, men, and children. A level above 500
nanograms/milliliter of AFP in adults can be indicative of hepatocellular carcinoma,
germ cell tumors, and metastatic cancers of the liver.
A peptide derived from AFP that is referred to as AFPep is claimed to possess anti-cancer
properties. See also
Tumor marker AFP-L3
References
Further reading
External links alpha-Fetoproteins at the US National Library
of Medicine Medical Subject Headings This article incorporates text from the United
States National Library of Medicine, which is in the public domain.