Ganong's Review of Medical Physiology, 23rd Edition

396 SECTION IV Endocrine & Reproductive Physiology
Y + 22
Bipotential
gonad
Embryonic
testis
Adult
testis
SRY
MALE
44
XY
X
22
MIS
DHT
DHT
FIGURE 25–6 Diagrammatic summary of normal sex determination, differentiation, and development in humans. MIS, müllerian
inhibiting substance; T, testosterone; DHT, dihydrotestosterone.
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
No female
internal
genitalia
Male
internal
genitalia
Male
external
genitalia
"Male
brain"
Bipotential
primordia
Male
secondary sex
characteristics
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 effects
on behavior. However, women with adrenogenital syndrome
due to congenital adrenocortical enzyme deficiency
(see Chapter 22) develop normal menstrual cycles when treated
with cortisol. Thus, the human, like the monkey, appears to
retain the cyclical pattern of gonadotropin secretion despite
exposure to androgens in utero.
T
T
X + 22
Bipotential
gonad
Embryonic
ovary
Adult
ovary
FEMALE
44
XX
Estrogens
X
22
Female
internal
genitalia
Female
external
genitalia
"Female
brain"
Female
secondary sex
characteristics
ABERRANT SEXUAL DIFFERENTIATION
Chromosomal Abnormalities
Bipotential
primordia
From the preceding discussion, it might be expected that abnormalities
of sexual development could be caused by genetic
or hormonal abnormalities as well as by other nonspecific teratogenic
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 division
in meiosis results in distinct defects (see Clinical Box
25–1). Meiosis is a two-stage process, and although nondisjunction
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 mosaicism
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