Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 25The Gonads: Development & Function of the Reproductive System 425

Other Placental Hormones

In addition to hCG, hCS, progesterone, and estrogens, the pla-
centa secretes other hormones. Human placental fragments
probably produce proopiomelanocortin (POMC). In culture,
they release corticotropin-releasing hormone (CRH), β-
endorphin, α-melanocyte-stimulating hormone (MSH), and
dynorphin A, all of which appear to be identical to their hypo-
thalamic counterparts. They also secrete GnRH and inhibin,
and since GnRH stimulates and inhibin inhibits hCG secre-
tion, locally produced GnRH and inhibin may act in a paracrine
fashion to regulate hCG secretion. The trophoblast cells and
amnion cells also secrete leptin, and moderate amounts of this
satiety hormone enter the maternal circulation. Some also en-
ters the amniotic fluid. Its function in pregnancy is unknown.
The placenta also secretes prolactin in a number of forms.
Finally, the placenta secretes the α subunits of hCG, and the
plasma concentration of free α subunits rises throughout
pregnancy. These α subunits acquire a carbohydrate composi-
tion that makes them unable to combine with β subunits, and
their prominence suggests that they have a function of their
own. It is interesting in this regard that the secretion of the
prolactin produced by the endometrium also appears to
increase throughout pregnancy, and it may be that the circu-
lating α subunits stimulate endometrial prolactin secretion.
The cytotrophoblast of the human chorion contains prore-
nin (see Chapter 39). A large amount of prorenin is also
present in amniotic fluid, but its function in this location is
unknown.

Fetoplacental Unit

The fetus and the placenta interact in the formation of steroid
hormones. The placenta synthesizes pregnenolone and proges-
terone from cholesterol. Some of the progesterone enters the fe-
tal circulation and provides the substrate for the formation of
cortisol and corticosterone in the fetal adrenal glands (Figure
25–34). Some of the pregnenolone enters the fetus and, along
with pregnenolone synthesized in the fetal liver, is the substrate
for the formation of dehydroepiandrosterone sulfate (DHEAS)
and 16-hydroxydehydroepiandrosterone sulfate (16-OHDH-
EAS) in the fetal adrenal. Some 16-hydroxylation also occurs in
the fetal liver. DHEAS and 16-OHDHEAS are transported back
to the placenta, where DHEAS forms estradiol and 16-OHDH-
EAS forms estriol. The principal estrogen formed is estriol, and
since fetal 16-OHDHEAS is the principal substrate for the es-
trogens, the urinary estriol excretion of the mother can be mon-
itored as an index of the state of the fetus.

Parturition

The duration of pregnancy in humans averages 270 d from
fertilization (284 d from the first day of the menstrual period
preceding conception). Irregular uterine contractions increase
in frequency in the last month of pregnancy.
The difference between the body of the uterus and the cer-
vix becomes evident at the time of delivery. The cervix, which

is firm in the nonpregnant state and throughout pregnancy

until near the time of delivery, softens and dilates, while the

body of the uterus contracts and expels the fetus.

There is still considerable uncertainty about the mecha-

nisms responsible for the onset of labor. One factor is the

increase in circulating estrogens produced by increased circu-

lating DHEAS. This makes the uterus more excitable, increases

the number of gap junctions between myometrial cells, and

causes production of more prostaglandins, which in turn cause

uterine contractions. In humans, CRH secretion by the fetal

hypothalamus increases and is supplemented by increased pla-

cental production of CRH. This increases circulating adreno-

corticotropic hormone (ACTH) in the fetus, and the resulting

increase in cortisol hastens the maturation of the respiratory

system. Thus, in a sense, the fetus picks the time to be born by

increasing CRH secretion.

The number of oxytocin receptors in the myometrium and

the decidua (the endometrium of pregnancy) increases more

than 100-fold during pregnancy and reaches a peak during

early labor. Estrogens increase the number of oxytocin recep-

tors, and uterine distention late in pregnancy may also

increase their formation. In early labor, the oxytocin concen-

tration in maternal plasma is not elevated from the prelabor

value of about 25 pg/mL. It is possible that the marked

increase in oxytocin receptors causes the uterus to respond to

normal plasma oxytocin concentrations. However, at least in

rats, the amount of oxytocin mRNA in the uterus increases,

reaching a peak at term; this suggests that locally produced

oxytocin also participates in the process.

Premature onset of labor is a problem because premature

infants have a high mortality rate and often require intensive,

expensive care. Intramuscular 17α-hydroxyprogesterone causes

a significant decrease in the incidence of premature labor. The

mechanism by which it exerts its effect is uncertain, but it may

be that the steroid provides a stable level of circulating

progesterone. Progesterone relaxes uterine smooth muscle,

inhibits the action of oxytocin on the muscle, and reduces

FIGURE 25–34 Interactions between the placenta and the

fetal adrenal cortex in the production of steroids.

Placenta

Cholesterol

Pregnenolone DHEAS

Fetal Adrenal

16-OHDHEAS

Cortisol,

corticosterone

Progesterone

Estradiol DHEAS

Estriol 16-OHDHEAS