424 SECTION IVEndocrine & Reproductive Physiology
burrows into it (implantation). The implantation site is usually
on the dorsal wall of the uterus. A placenta then develops, and
the trophoblast remains associated with it.
Failure to Reject the “Fetal Graft”
It should be noted that the fetus and the mother are two genet-
ically distinct individuals, and the fetus is in effect a transplant
of foreign tissue in the mother. However, the transplant is tol-
erated, and the rejection reaction that is characteristically pro-
duced when other foreign tissues are transplanted (see
Chapter 3) fails to occur. The way the “fetal graft” is protected
is unknown. However, one explanation may be that the pla-
cental trophoblast, which separates maternal and fetal tissues,
does not express the polymorphic class I and class II MHC
genes and instead expresses HLA-G, a nonpolymorphic gene.
Therefore, antibodies against the fetal proteins do not devel-
op. In addition, there is a Fas ligand on the surface of the pla-
centa, and this bonds to T cells, causing them to undergo
apoptosis (see Chapter 3).
Infertility
The vexing clinical problem of infertility often requires exten-
sive investigation before a cause is found. In 30% of cases the
problem is in the man; in 45%, the problem is in the woman;
in 20%, both partners have a problem; and in 5% no cause can
be found. In vitro fertilization, that is, removing mature ova,
fertilizing them with sperm, and implanting one or more of
them in the uterus at the four-cell stage is of some value in
these cases. It has a 5–10% chance of producing a live birth.
Endocrine Changes
In all mammals, the corpus luteum in the ovary at the time of
fertilization fails to regress and instead enlarges in response to
stimulation by gonadotropic hormones secreted by the placen-
ta. The placental gonadotropin in humans is called human
chorionic gonadotropin (hCG). The enlarged corpus luteum
of pregnancy secretes estrogens, progesterone, and relaxin. The
relaxin helps maintain pregnancy by inhibiting myometrial
contractions. In most species, removal of the ovaries at any time
during pregnancy precipitates abortion. In humans, however,
the placenta produces sufficient estrogen and progesterone
from maternal and fetal precursors to take over the function of
the corpus luteum after the sixth week of pregnancy. Ovariecto-
my before the sixth week leads to abortion, but ovariectomy
thereafter has no effect on the pregnancy. The function of the
corpus luteum begins to decline after 8 wk of pregnancy, but it
persists throughout pregnancy. hCG secretion decreases after
an initial marked rise, but estrogen and progesterone secretion
increase until just before parturition (Table 25–9).
Human Chorionic Gonadotropin
hCG is a glycoprotein that contains galactose and hexosamine.
It is produced by the syncytiotrophoblast. Like the pituitary
glycoprotein hormones, it is made up of α and β subunits.
hCG-α is identical to the α subunit of LH, FSH, and TSH. The
molecular weight of hCG-α is 18,000, and that of hCG-β is
28,000. hCG is primarily luteinizing and luteotropic and has
little FSH activity. It can be measured by radioimmunoassay
and detected in the blood as early as 6 d after conception. Its
presence in the urine in early pregnancy is the basis of the var-
ious laboratory tests for pregnancy, and it can sometimes be
detected in the urine as early as 14 d after conception. It ap-
pears to act on the same receptor as LH. hCG is not absolutely
specific for pregnancy. Small amounts are secreted by a variety
of gastrointestinal and other tumors in both sexes, and hCG
has been measured in individuals with suspected tumors as a
“tumor marker.” It also appears that the fetal liver and kidney
normally produce small amounts of hCG.Human Chorionic Somatomammotropin
The syncytiotrophoblast also secretes large amounts of a pro-
tein hormone that is lactogenic and has a small amount of
growth-stimulating activity. This hormone has been called
chorionic growth hormone-prolactin (CGP) and human
placental lactogen (hPL), but it is now generally called hu-
man chorionic somatomammotropin (hCS). The structure
of hCS is very similar to that of human growth hormone (see
Figure 24–3), and it appears that these two hormones and pro-
lactin evolved from a common progenitor hormone. Large
quantities of hCS are found in maternal blood, but very little
reaches the fetus. Secretion of growth hormone from the ma-
ternal pituitary is not increased during pregnancy and may ac-
tually be decreased by hCS. However, hCS has most of the
actions of growth hormone and apparently functions as a
“maternal growth hormone of pregnancy” to bring about the
nitrogen, potassium, and calcium retention, lipolysis, and de-
creased glucose utilization seen in this state. These latter two
actions divert glucose to the fetus. The amount of hCS secreted
is proportionate to the size of the placenta, which normally
weighs about one-sixth as much as the fetus, and low hCS le-
vels are a sign of placental insufficiency.TABLE 25–9 Hormone levels in human
maternal blood during normal pregnancy.HormoneApproximate
Peak Value Time of Peak Secretion
hCG 5 mg/mL First trimester
Relaxin 1 ng/mL First trimester
hCS 15 mg/mL Term
Estradiol 16 ng/mL Term
Estriol 14 ng/mL Term
Progesterone 190 ng/mL Term
Prolactin 200 ng/mL Term