Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 25The Gonads: Development & Function of the Reproductive System 417

Secretion

The concentration of estradiol in the plasma during the men-
strual cycle is shown in Figure 25–25. Almost all of this estro-
gen comes from the ovary, and two peaks of secretion occur:
one just before ovulation and one during the midluteal phase.
The estradiol secretion rate is 36 μg/d (133 nmol/d) in the ear-
ly follicular phase, 380 μg/d just before ovulation, and 250 μg/d
during the midluteal phase (Table 25–7). After menopause,
estrogen secretion declines to low levels.
As noted previously, the estradiol production rate in men is
about 50 μg/d (184 nmol/d).

Effects on the Female Genitalia

Estrogens facilitate the growth of the ovarian follicles and in-
crease the motility of the uterine tubes. Their role in the cyclic
changes in the endometrium, cervix, and vagina has been dis-
cussed previously. They increase uterine blood flow and have
important effects on the smooth muscle of the uterus. In im-
mature and castrated females, the uterus is small and the my-
ometrium atrophic and inactive. Estrogens increase the
amount of uterine muscle and its content of contractile pro-
teins. Under the influence of estrogens, the muscle becomes
more active and excitable, and action potentials in the individ-
ual fibers become more frequent. The “estrogen-dominated”
uterus is also more sensitive to oxytocin.
Chronic treatment with estrogens causes the endometrium
to hypertrophy. When estrogen therapy is discontinued,
sloughing takes place with withdrawal bleeding. Some “break-
through” bleeding may occur during treatment when estrogens
are given for long periods.

Effects on Endocrine Organs

Estrogens decrease FSH secretion. Under some circumstanc-

es, they inhibit LH secretion (negative feedback); in other cir-

cumstances, they increase LH secretion (positive feedback).

Women are sometimes given large doses of estrogens for 4 to

6 d to prevent conception after coitus during the fertile period

(postcoital or “morning-after” contraception). However, in

this instance, pregnancy is probably prevented by interference

with implantation of the ovum rather than changes in gonad-

otropin secretion.

Estrogens cause increased secretion of angiotensinogen and

thyroid-binding globulin. They exert an important protein

anabolic effect in chickens and cattle, possibly by stimulating

the secretion of androgens from the adrenal, and estrogen

treatment has been used commercially to increase the weight

of domestic animals. They cause epiphysial closure in humans

(see Chapter 23).

Effects on the Central Nervous System

The estrogens are responsible for estrous behavior in animals,

and they increase libido in humans. They apparently exert

this action by a direct effect on certain neurons in the hypo-

thalamus (Figure 25–28). Estrogens also increase the prolifer-

ation of dendrites on neurons and the number of synaptic

knobs in rats.

Effects on the Breasts

Estrogens produce duct growth in the breasts and are largely re-

sponsible for breast enlargement at puberty in girls; they have

been called the growth hormones of the breast. They are re-

sponsible for the pigmentation of the areolas, although pigmen-

tation usually becomes more intense during the first pregnancy

than it does at puberty. The role of the estrogens in the overall

control of breast growth and lactation is discussed below.

TABLE 25–7 Twenty-four-hour production
rates of sex steroids in women at different
stages of the menstrual cycle.

Sex Steroids

Early

Follicular Preovulatory Midluteal

Progesterone (mg) 1.0 4.0 25.0

17-hydroxyprogesterone

(mg)

0.5 4.0 4.0

Dehydroepiandrosterone

(mg)

7.0 7.0 7.0

Androstenedione (mg) 2.6 4.7 3.4

Testosterone (μg) 144.0 171.0 126.0

Estrone (μg) 50.0 350.0 250.0

Estradiol (μg) 36.0 380.0 250.0

Modified and reproduced, with permission, from Yen SSC, Jaffe RB, Barbieri RL:
Reproductive Endocrinology, 4th ed. Saunders, 1999.

FIGURE 25–28 Loci where implantations of estrogen in the

hypothalamus affect ovarian weight and sexual behavior in rats,

projected on a sagittal section of the hypothalamus. The implants

that stimulate sex behavior are located in the suprachiasmatic area

above the optic chiasm (blue area), whereas ovarian atrophy is pro-

duced by implants in the arcuate nucleus and surrounding ventral hy-

pothalamus (red). MB, mamillary body.

Third

ventricle

Massa

intermedia

Midbrain

MB

Pituitary

Optic

chiasm