Intersexuality

Thedevelopment of the gonadal anlagento

ovaries and testes is fixed by the presence or
absence of thetestis-determining factor(TDF),
which is encoded on the sex determining re-
gion of the Y chromosome (SRY) and is respon-
sible for testicular development (A 1). Ova-
ries develop if TDF is absent (A 2). The go-
nads determine the formation of female and
malesexual hormones. Testosterone is formed
in the Leydig cells of the testes, while anti-
Mller hormones are formed in the Sertoli
cells (Mller inhibition factor [MIF];A 1).
However, not only androgens but also proges-
togens (some of them precursors of testoster-
one formation) and estradiol (predominantly
by peripheral transformation of testosterone)
9 Hormones
are formed in the male. Progestogens and es-
trogens and, to a lesser extent, also androgens
(mainly androstendion) are produced in the
ovaries (A 2).
The development of the Wolffian ducts to
internal male genitals(epididymis and vas
deferens) is stimulated by the androgens,
while the development of the Mller ducts to
form theinternal female genitals(fallopian
tubes, uterus, vagina) is suppressed by the
anti-Mller hormone from the Sertoli cells.
Theexternal sexual characteristicsare deter-
mined, first and foremost, by the concentra-
tion of androgens (p. 272), whereby the de-
velopment of the female genitals and some of
the sexual characteristics is promoted by es-
trogens.
The sex of an individual can be defined on
the basis of thechromosomal set(XX or XY, re-
spectively), of thegonads(ovary or testis), of
theinternal organsor ofexternal appeareance.
Intersexualityoccurs when the various sex
characteristics have not developed unequivo-
cally or are more or less pronounced.
An abnormal chromsome set occurs, for ex-
ample, inKlinefelters syndrome(XXY), in
which the testes are formed in such a way
that spermatogenesis is possible, but androgen
production is impaired (A 3). The androgen
deficiency then leads to an inadequately male
appearance. Only mild clinical symptoms are
present in the XYY syndrome. A similar condi-
278tion prevails in theXX male syndrome, which
is probably due to translocation of an SRY-con-
taining Y chromosome fragment onto an X
chromsome. InTurners syndrome(XO) con-
nective tissue strands are formed in place of
normal ovaries and the external features are
more likely to be female (A 4). The condition
is characterized by a number of additional
malformations (e.g., of the heart and kidneys;
dwarfism, webbed neck).
In certainmutations of the SRY geneno
functional TDF is formed, despite the presence
of a male chromosome set (XY), and ovaries
develop (A 5).
Intrue hermaphroditismboth testes and
ovaries are simultaneously formed (A 6). An
XY/XO mosaic can be a cause. Translocation of
some parts of the Y chromosome, including of
the SRY gene, onto an X chromosome (as in the
XX male, see above) can lead to the formation
of bisexual gonads and the appearance of in-
tersexual sex characteristcs.
Inpseudohermaphroditismthe gonads cor-
respond to the chromosomal sex, but the sex
organs and secondary sex characteristics di-
verge or are not unequivocal. Inmale pseudo-
hermaphroditismintersexual or female sex
characteristics are present (A 7). A gonado-
tropin deficiency may be a cause, for example
when gonadotropin release is suppressed due
to an increased formation of female sexual
hormones by a tumor. Other causes can be de-
fects in the gonadotropin receptor, aplasia of
the Leydig cells, enzyme defects of testoster-
one synthesis (p. 264), defective testes,
absent conversion of testosterone into dihy-
drotestosterone (reductase deficiency), or de-
fective androgen receptors (p. 272). In rare
cases the formation of the female genitals
may not be suppressed owing to a defect in
the release or action of the anti-Mller hor-
mone.Female pseudohermaphroditism(
A 8) can be the result of iatrogenic administra-
tion or increased formation of androgens, for
example in an androgen-producing tumor, or
can be due to an enzymatic defect in adreno-
cortical hormone synthesis, or a defect of aro-
matase, which transforms androstendion or
rather testosterone into estrogens (p. 264).

Silbernagl/Lang, Color Atlas of Pathophysiology 2000 Thieme
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