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Ganong's Review of Medical Physiology, 23rd Edition

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Initiation <strong>of</strong> Lactation after Delivery<br />

The breasts enlarge during pregnancy in response to high circulating<br />

levels <strong>of</strong> estrogens, progesterone, prolactin, and possibly<br />

hCG. Some milk is secreted into the ducts as early as the<br />

fifth month, but the amounts are small compared with the<br />

surge <strong>of</strong> milk secretion that follows delivery. In most animals,<br />

milk is secreted within an hour after delivery, but in women it<br />

takes 1 to 3 d for the milk to “come in.”<br />

After expulsion <strong>of</strong> the placenta at parturition, the levels <strong>of</strong><br />

circulating estrogens and progesterone abruptly decline. The<br />

drop in circulating estrogen initiates lactation. Prolactin and<br />

estrogen synergize in producing breast growth, but estrogen<br />

antagonizes the milk-producing effect <strong>of</strong> prolactin on the<br />

breast. Indeed, in women who do not wish to nurse their<br />

babies, estrogens may be administered to stop lactation.<br />

Suckling not only evokes reflex oxytocin release and milk<br />

ejection, it also maintains and augments the secretion <strong>of</strong> milk<br />

because <strong>of</strong> the stimulation <strong>of</strong> prolactin secretion produced by<br />

suckling.<br />

Effect <strong>of</strong> Lactation on Menstrual Cycles<br />

Women who do not nurse their infants usually have their first<br />

menstrual period 6 wk after delivery. However, women who<br />

nurse regularly have amenorrhea for 25 to 30 wk. Nursing<br />

stimulates prolactin secretion, and evidence suggests that prolactin<br />

inhibits GnRH secretion, inhibits the action <strong>of</strong> GnRH<br />

on the pituitary, and antagonizes the action <strong>of</strong> gonadotropins<br />

on the ovaries. Ovulation is inhibited, and the ovaries are inactive,<br />

so estrogen and progesterone output falls to low levels.<br />

Consequently, only 5–10% <strong>of</strong> women become pregnant again<br />

during the suckling period, and nursing has long been known<br />

to be an important, if only partly effective, method <strong>of</strong> birth<br />

control. Furthermore, almost 50% <strong>of</strong> the cycles in the first 6<br />

mo after resumption <strong>of</strong> menses are anovulatory (see Clinical<br />

Box 25–6).<br />

Gynecomastia<br />

Breast development in the male is called gynecomastia. It may<br />

be unilateral but is more commonly bilateral. It is common,<br />

occurring in about 75% <strong>of</strong> newborns because <strong>of</strong> transplacental<br />

passage <strong>of</strong> maternal estrogens. It also occurs in mild, transient<br />

form in 70% <strong>of</strong> normal boys at the time <strong>of</strong> puberty and in<br />

many men over the age <strong>of</strong> 50. It occurs in androgen resistance.<br />

It is a complication <strong>of</strong> estrogen therapy and is seen in patients<br />

with estrogen-secreting tumors. It is found in a wide variety <strong>of</strong><br />

seemingly unrelated conditions, including eunuchoidism, hyperthyroidism,<br />

and cirrhosis <strong>of</strong> the liver. Digitalis can produce<br />

it, apparently because cardiac glycosides are weakly estrogenic.<br />

It can also be caused by many other drugs. It has been seen<br />

in malnourished prisoners <strong>of</strong> war, but only after they were liberated<br />

and eating an adequate diet. A feature common to<br />

many and perhaps all cases <strong>of</strong> gynecomastia is an increase in<br />

the plasma estrogen:androgen ratio due to either increased<br />

circulating estrogens or decreased circulating androgens.<br />

CHAPTER 25 The Gonads: Development & Function <strong>of</strong> the Reproductive System 427<br />

CLINICAL BOX 25–6<br />

Chiari–Frommel Syndrome<br />

An interesting, although rare, condition is persistence <strong>of</strong> lactation<br />

(galactorrhea) and amenorrhea in women who do<br />

not nurse after delivery. This condition, called the Chiari–<br />

Frommel syndrome, may be associated with some genital<br />

atrophy and is due to persistent prolactin secretion without<br />

the secretion <strong>of</strong> the FSH and LH necessary to produce maturation<br />

<strong>of</strong> new follicles and ovulation. A similar pattern <strong>of</strong> galactorrhea<br />

and amenorrhea with high circulating prolactin<br />

levels is seen in nonpregnant women with chromophobe<br />

pituitary tumors and in women in whom the pituitary stalk<br />

has been sectioned during treatment <strong>of</strong> cancer.<br />

HORMONES & CANCER<br />

About 35% <strong>of</strong> carcinomas <strong>of</strong> the breast in women <strong>of</strong> childbearing<br />

age are estrogen-dependent; their continued growth depends<br />

on the presence <strong>of</strong> estrogens in the circulation. The<br />

tumors are not cured by decreasing estrogen secretion, but<br />

symptoms are dramatically relieved, and the tumor regresses<br />

for months or years before recurring. Women with estrogendependent<br />

tumors <strong>of</strong>ten have a remission when their ovaries<br />

are removed. Inhibition <strong>of</strong> the action <strong>of</strong> estrogens with tamoxifen<br />

also produces remissions, and inhibition <strong>of</strong> estrogen formation<br />

with drugs that inhibit aromatase (Figure 25–26) is<br />

even more effective.<br />

Some carcinomas <strong>of</strong> the prostate are androgen-dependent<br />

and regress temporarily after the removal <strong>of</strong> the testes or<br />

treatment with GnRH agonists in doses that are sufficient to<br />

produce down-regulation <strong>of</strong> the GnRH receptors on gonadotropes<br />

and decrease LH secretion.<br />

CHAPTER SUMMARY<br />

■ Differences between males and females depend primarily on a<br />

single chromosome (the Y chromosome) and a single pair <strong>of</strong><br />

endocrine structures (the gonads); testes in the male and ovaries<br />

in the female.<br />

■ The gonads have a dual function: the production <strong>of</strong> germ cells<br />

(gametogenesis) and the secretion <strong>of</strong> sex hormones. The testes<br />

secrete large amounts <strong>of</strong> androgens, principally testosterone, but<br />

they also secrete small amounts <strong>of</strong> estrogens. The ovaries secrete<br />

large amounts <strong>of</strong> estrogens and small amounts <strong>of</strong> androgens.<br />

■ Spermatogonia develop into mature spermatozoa that start in<br />

the seminiferous tubules in a process called spermatogenesis.<br />

This is a multistep process that includes maturation <strong>of</strong><br />

spermatogonia into primary spermatocytes, which undergo<br />

meiotic division, resulting in haploid secondary spermatocytes<br />

and several further divisions result in spermatids. Each<br />

cell division from a spermatogonium to a spermatid is incomplete<br />

with cells remaining connected via cytoplasmic bridges.<br />

Spermatids eventually mature into motile spermatozoa to

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