Chemistry Reference
In-Depth Information
blood supply to the invading placenta and optimal nutrition to the fetus.
hCG also generates a wide array of actions to prevent rejection of the
fetoplacental tissue.
3
ii) Hyperglycosylated hCG is produced by cytotrophoblast cells during
implantation of pregnancy. hCG and hyperglycosylated hCG seemingly
act together to promote the growth and differentiation of trophoblast
cells or formation of the placenta villous structures.
3
However,
hyperglycosylated hCG becomes a malignant glycoform of the hormone
which promotes growth and invasion by choriocarcinoma cells. These
glycoforms appears to act by antagonizing a cytotrophoblast TGFb
receptor and blocking apoptosis to promote invasion of cancer cells.
4
iii) The free b-subunit was identified as a characteristic metastatic
phenotype marker
5,6
and correlated with poor prognosis and tumors that
will rapidly progress to metastasis.
7
As hyperglycosylated hCG, free
b-subunit promotes cancer cell growth and malignancy by blocking
apoptosis.
7,8
iv) Pituitary hCG is a sulfated variant of hCG produced by the gona-
dotrope cells of the anterior pituitary. This form is produced at very low
levels in men and in women, is present in pulses in the luteal and fol-
licular phases of the menstrual cycle which paralleled LH levels .
9,10
It is
still not clear whether pituitary hCG just assists LH or has specific
functions during the menstrual cycle. Laurence A. Cole from hCG Ref-
erence Service, (Albuquerque, USA) suggests that production of pituitary
hCG could be explained by proximity of LH and hCG b-subunits on
chromosome 19.
3,11
2.4 Free a-subunit
The a-subunit is also secreted as a free molecule by the pituitary
throughout the menstrual cycle and by the placenta during pregnancy. It
may circulate in blood independently of the intact hormones.
12,13
While
hCG-b remains in a lower serum level throughout the pregnancy,
a-subunit increases gradually to reaching its maximum at term.
14
Moreover, it has been shown that a-subunit function is independent of
the dimeric hormones since it induces differentiation of the lactotropic
cells from the anterior pituitary,
15
stimulates release of prolactin
16,17
and
acts synergistically with progesterone to induce more rapid decidualiza-
tion in the pregnant uterus.
13
Plasma levels of the free a subunit are high during the neonatal period,
decreases to a nadir at the age of six years and increases significantly with
puberty and menopause. During menstrual cycle, a typical preovulatory
surge is seen simultaneous with the LH surge.
18
3 Structure of gonadotropins
Human gonadotropins are ab heterodimers closely related in structure.
Each hormone consists in a common a-subunit of 92 amino acids
(13kDa) and a specific b-subunit which confers hormone-specific features
to the dimer (FSH: 129 amino acids, 14.7kDa; LH: 141 amino acids,
15.3kDa; hCG: 165 amino acids, 17.7kDa). All are highly polymorphic
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