410 SECTION IVEndocrine & Reproductive Physiology
biologic activity, but the relation of follistatins to inhibin and
their physiologic function remain unsettled.
Steroid Feedback
A current “working hypothesis” of the way the functions of the
testes are regulated by steroids is shown in Figure 25–20. Cas-
tration is followed by a rise in the pituitary content and secre-
tion of FSH and LH, and hypothalamic lesions prevent this
rise. Testosterone inhibits LH secretion by acting directly on
the anterior pituitary and by inhibiting the secretion of GnRH
from the hypothalamus. Inhibin acts directly on the anterior
pituitary to inhibit FSH secretion.
In response to LH, some of the testosterone secreted from the
Leydig cells bathes the seminiferous epithelium and provides
the high local concentration of androgen to the Sertoli cells that
is necessary for normal spermatogenesis. Systemically adminis-
tered testosterone does not raise the androgen level in the testes
to as great a degree, and it inhibits LH secretion. Consequently,
the net effect of systemically administered testosterone is gen-
erally a decrease in sperm count. Testosterone therapy has been
suggested as a means of male contraception. However, the dose
of testosterone needed to suppress spermatogenesis causes
sodium and water retention. The possible use of inhibins as
male contraceptives is now being explored.
ABNORMALITIES OF
TESTICULAR FUNCTION
Cryptorchidism
The testes develop in the abdominal cavity and normally mi-
grate to the scrotum during fetal development. Testicular de-
scent to the inguinal region depends on MIS, and descent
from the inguinal region to the scrotum depends on other fac-
tors. Descent is incomplete on one or, less commonly, both
sides in 10% of newborn males, with the testes remaining in
the abdominal cavity or inguinal canal. Gonadotropic hor-
mone treatment speeds descent in some cases, or the defect
can be corrected surgically. Spontaneous descent of the testes
is the rule, and the proportion of boys with undescended testes
(cryptorchidism) falls to 2% at age 1 y and 0.3% after puberty.
However, early treatment is now recommended despite these
figures because the incidence of malignant tumors is higher in
undescended than in scrotal testes and because after puberty
the higher temperature in the abdomen eventually causes irre-
versible damage to the spermatogenic epithelium.Male Hypogonadism
The clinical picture of male hypogonadism depends on
whether testicular deficiency develops before or after puberty.
In adults, if it is due to testicular disease, circulating gonado-
tropin levels are elevated (hypergonadotropic hypogonad-
ism); if it is secondary to disorders of the pituitary or the
hypothalamus (eg, Kallmann syndrome), circulating gonado-
tropin levels are depressed (hypogonadotropic hypogonad-
ism). If the endocrine function of the testes is lost in
adulthood, the secondary sex characteristics regress slowly be-
cause it takes very little androgen to maintain them once they
are established. The growth of the larynx during adolescence
is permanent, and the voice remains deep. Men castrated in
adulthood suffer some loss of libido, although the ability to
copulate persists for some time. They occasionally have hot
flushes and are generally more irritable, passive, and de-
pressed than men with intact testes. When the Leydig cell de-
ficiency dates from childhood, the clinical picture is that of
eunuchoidism. Eunuchoid individuals over the age of 20 are
characteristically tall, although not as tall as hyperpituitary gi-
ants, because their epiphyses remain open and some growth
continues past the normal age of puberty. They have narrow
shoulders and small muscles, a body configuration resembling
that of the adult female. The genitalia are small and the voice
high-pitched. Pubic hair and axillary hair are present because
of adrenocortical androgen secretion. However, the hair is
sparse, and the pubic hair has the female “triangle with the
base up” distribution rather than the “triangle with the base
down” pattern (male escutcheon) seen in normal males.Androgen-Secreting Tumors
“Hyperfunction” of the testes in the absence of tumor forma-
tion is not a recognized entity. Androgen-secreting Leydig cell
tumors are rare and cause detectable endocrine symptoms
only in prepubertal boys, who develop precocious pseudopu-
berty (Table 25–2).FIGURE 25–20 Postulated interrelationships between the
hypothalamus, anterior pituitary, and testes. Solid arrows indicate
excitatory effects; dashed arrows indicate inhibitory effects.
GnRHLHAndrogenic
and anabolic
effectsTestosteroneFSHLeydig
cellsSertoli
cellsInhibin BHypothalamusAnterior
pituitaryTestis