Patients with ectopic pregnancy frequently exhibit ab-
dominal pain with amenorrhea. By far the most common
cause is an impaired fallopian tubal function. The tubal
pathology can result from pelvic infection, endometriosis,
or previous surgery. The implanted embryo commonly
dies in the early weeks of pregnancy. Tubal rupture and the
associated bleeding require emergency care. Thus, early
diagnosis is essential and consists of serial measurements
of serum levels of hCG using antibodies specific for the
subunits of hCG (/3-hCG) and serum progesterone, and
pelvic ultrasonography. In ectopic pregnancy, the serum
/1-hCG levels are lower than those observed at the
same gestational age in a normal pregnancy. A serum
progesterone level of 25 ng/mL (79.5 nM/L) or higher
excludes ectopic pregnancy with 97.5% sensitivity. The
treatment for ectopic pregnancy consists of either surgery
to remove the embryonic tissue or medical treatment
with methrotrexate, a folic acid antagonist. Methotrexate
inhibits both
de novo
purine and pyrimidine nucleotide
(Chapter 27),
and cell
multiplication of the actively proliferating
Placental Steroids
The absence of progesterone is incompatible with the
gravid state. Progesterone acts in three ways to maintain
1. It maintains placental viability, thus ensuring
adequate exchange of substances between maternal
and fetal compartments;
2. It maintains perfusion of the decidua basalis
(maternal placenta), presumably by inhibiting the
formation of vasoconstrictive prostaglandins; and
3. It diminishes myometrial contractility, possibly by
increasing the resting membrane potential or by
inhibiting the formation of prostaglandins Ei and F
(Chapter 18). The placenta is the major site of
conversion of cholesterol to progesterone after the
sixth week; however, it is not capable of synthesizing
cholesterol from acetate. Moreover, the placenta lacks
CYP 17 and CYP 21, which explains why the major
steroid it produces is progesterone (Figure 34-5).
Although the placenta cannot process cholesterol
beyond progesterone, it contains some important
steroid-modifying enzymes which enable it to
produce substantial amounts of estrogen.
Small amounts of estrogen are required for maintenance
of pregnancy because estrogen maintains tissue respon-
siveness to progesterone. The placenta forms estrogen
from androgenic steroids. The major androgen used is
M ate rn a l circ u la tio n
_________ P la c e n ta
C h o le s te ro l
— C h o le s te ro l
P r e g n e n o lo n e
3 ß -H SD H
P r o g e s te r o n e
P r o g e s te r o n e
F e ta l circu latio n
C h o le ste ro l
P re g n a n e d io l
(e x c re te d in u rin e)
F I G U R E 3 4 - 5
Placental synthesis of progesterone. The placenta contains cholesterol
side-chain cleavage enzyme (CYP11A) and 3/1-hydroxysteroid
dehydrogenase (3/i-HSDH), which enable it to form progesterone from
cholesterol. However, it does not make cholesterol
d e n o vo
and relies
mainly on the maternal cholesterol pool for substrate. Progesterone exerts
its effects on the uterus and placental vasculature and enters the maternal
circulation. Maternal tissues reduce progesterone predominantly to
pregnanediol, which is the major metabolite of progesterone in maternal
déhydroépiandrostérone (DHEA), derived mainly from
the fetal compartment in the form of DHEAS (DHEA sul-
fate). The source of DHEAS is the fetal zone of the fetal
adrenal gland, which, produces mainly DHEAS because
it lacks 3/YHSDH (Chapter 30). The placenta takes up
DHEAS from the fetal circulation and, by the action of
placental sulfatase, liberates DHEA, which is then aroma-
tized into estrone (Ei ) (Figure 34-6). Some Ei is converted
to E
by placental 17-HSDH, and both are released into
the maternal circulation. A substantial fraction of DHEAS
produced by the fetal zone is taken up by the fetal liver,
which detoxifies it to 16
-hydroxy-DHEAS. The placenta
also processes this metabolite through the aromatase sys-
tem, and the product is estriol (E
), a weak estrogen that
is not produced in significant amounts in the nongravid
state. The circulating level of E
is an important index of
fetal-placental function because its production depends on
normal functioning of the fetal adrenal, fetal liver, and the
placenta. It is therefore used clinically as a diagnostic tool.
Human Placental Lactogen (hPL)
Human placental lactogen (hPL) is produced by the syn-
cytiotrophoblast from about the time when production of
hCG begins to diminish. Production of hPL is proportional
to placental growth, and its level reflects placental well-
being. hPL exerts GH-like effects in both fetal and ma-
ternal compartments. In the fetus, it promotes formation
of insulin-like growth factor and growth factors believed
to promote growth of most, if not all, fetal tissues. In the
mother, hPL promotes nitrogen retention and utilization
of free fatty acids, and it creates a state of mild insulin
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