Ganong's Review of Medical Physiology, 23rd Edition

396
SECTION IV
Endocrine & Reproductive Physiology

as in adult men, that is, about 2 ng/mL. The functions of MIS
after early embryonic life are unsettled, but it is probably
involved in germ cell maturation in both sexes and in control
of testicular descent in boys.

Development of the Brain

At least in some species, the development of the brain as well
as the external genitalia is affected by androgens early in life.
In rats, a brief exposure to androgens during the first few days
of life causes the male pattern of sexual behavior and the male
pattern of hypothalamic control of gonadotropin secretion to
develop after puberty. In the absence of androgens, female
patterns develop (see Chapter 18). In monkeys, similar effects
on sexual behavior are produced by exposure to androgens in
utero, but the pattern of gonadotropin secretion remains
cyclical. Early exposure of female human fetuses to androgens
also appears to cause subtle but significant masculinizing ef-
fects on behavior. However, women with adrenogenital syn-
drome due to congenital adrenocortical enzyme deficiency
(see Chapter 22) develop normal menstrual cycles when treat-
ed with cortisol. Thus, the human, like the monkey, appears to
retain the cyclical pattern of gonadotropin secretion despite
exposure to androgens in utero.

ABERRANT SEXUAL DIFFERENTIATION

Chromosomal Abnormalities

From the preceding discussion, it might be expected that ab-

normalities of sexual development could be caused by genetic

or hormonal abnormalities as well as by other nonspecific ter-

atogenic influences, and this is indeed the case. The major

classes of abnormalities are listed in Table 25–1.

Nondisjunction of sex chromosomes during the first divi-

sion in meiosis results in distinct defects (see Clinical Box

25–1). Meiosis is a two-stage process, and although nondis-

junction usually occurs during the first meiotic division, it can

occur in the second, producing more complex chromosomal

abnormalities. In addition, nondisjunction or simple loss of a

sex chromosome can occur during the early mitotic divisions

after fertilization. The result of faulty mitoses in the early

zygote is the production of

mosaicism,

in which two or more

populations of cells have different chromosome complements.

True hermaphroditism,

the condition in which the individual

has both ovaries and testes, is probably due to XX/XY mosa-

icism and related mosaic patterns, although other genetic

aberrations are possible.

Chromosomal abnormalities also include transposition of

parts of chromosomes to other chromosomes. Rarely, genetic

males are found to have the XX karyotype because the short

FIGURE 25–6
Diagrammatic summary of normal sex determination, differentiation, and development in humans.
MIS, müllerian
inhibiting substance; T, testosterone; DHT, dihydrotestosterone.

Bipotential

gonad

Embryonic

testis

Adult

testis

SRY

No female

internal

genitalia

Male

internal

genitalia

Male

external

genitalia

"Male

brain"

Male

secondary sex

characteristics

Bipotential

primordia

DHT

DHT

T

MIS

44

XY

Y + 22

X

22

X

22

MALE

Bipotential

gonad

Embryonic

ovary

Adult

ovary

Female

internal

genitalia

Female

external

genitalia

"Female

brain"

Female

secondary sex

characteristics

Bipotential

primordia

Estrogens

44

XX

X + 22

FEMALE

T