612
Chapter 17
conversion is catalyzed by the enzyme
5
`
-reductase,
which
is expressed in a wide variety of androgen target tissues. In
certain other target cells (e.g., the brain), testosterone is
transformed not to dihydrotestosterone but to estradiol,
which is the active hormone in these cells. The enzyme aro-
matase catalyzes this conversion. Note in this latter case that
the “male” sex hormone must be converted to the “female”
sex hormone to be active in the male. The fact that, depend-
ing on the target cells, testosterone may act as testosterone,
dihydrotestosterone, or estradiol has important pathophysi-
ological implications because some men lack 5
α
-reductase or
aromatase in some tissues. Therefore, they will exhibit certain
signs of testosterone defi ciency but not others. For example,
an XY fetus with 5
α
-reductase defi
ciency will have normal
differentiation of male reproductive duct structures (an effect
of testosterone per se) but will not have normal development
of external male genitalia, which requires DHT.
Therapy for
prostate cancer
makes use of these facts:
prostate cancer cells are stimulated by dihydrotestosterone,
so the cancer can be treated with inhibitors of 5
α
-reductase.
Furthermore,
male pattern baldness
may also be treated with
5
α
-reductase inhibitors because DHT tends to promote hair
loss from the scalp.
Accessory Reproductive Organs
The fetal differentiation, and later growth and function of the
entire male duct system, glands, and penis all depend upon
testosterone. Following
castration
(removal of the gonads) in
the adult male, all the accessory reproductive organs decrease
in size, the glands markedly reduce their secretion rates, and
the smooth-muscle activity of the ducts is diminished. Sex
drive (
libido
), erection, and ejaculation are usually impaired.
These defects disappear upon the administration of testoster-
one. This also applies to
hypogonadism
,
which is described at
the end of this section.
Puberty
Puberty
is the period during which the reproductive organs
mature and reproduction becomes possible. In males, this
usually occurs between 12 and 16 years of age. Surprisingly,
some of the fi rst signs of puberty are due not to gonadal ste-
roids but to increased secretion of adrenal androgens, prob-
ably under the stimulation of adrenocorticotropic hormone
(ACTH). These androgens cause the very early development
of pubic and axillary (armpit) hair, as well as the early stages
of the pubertal growth spurt in concert with growth hormone
and insulin-like growth factor I (Chapter 11). All other devel-
opments in puberty, however, refl ect increased activity of the
hypothalamic-anterior pituitary-gonadal axis.
Increased GnRH secretion at puberty causes increased
secretion of pituitary gonadotropins, which stimulate the
seminiferous tubules and testosterone secretion. Testosterone,
in addition to its critical role in spermatogenesis, induces the
pubertal changes that occur in the accessory reproductive
organs, secondary sex characteristics, and sex drive. The mech-
anism of the brain change that results in increased GnRH
secretion at puberty remains unknown. One important event
is that the brain becomes less sensitive to the negative feed-
back effects of gonadal hormones at the time of puberty.
Secondary Sex Characteristics and Growth
Virtually all the male secondary sex characteristics are depen-
dent on testosterone and its metabolite, DHT. For example, a
male castrated before puberty has minimal facial, underarm,
or pubic hair. Other androgen-dependent secondary sexual
characteristics are deepening of the voice resulting from the
growth of the larynx, thick secretion of the skin oil glands
(often causing acne), and the masculine pattern of fat distribu-
tion. Androgens also stimulate bone growth, mostly through
the stimulation of growth hormone secretion. Ultimately,
however, androgens terminate bone growth by causing closure
of the bones’ epiphyseal plates. Androgens are “anabolic ste-
roids” in that they exert a direct stimulatory effect on protein
synthesis in muscle. Finally, androgens stimulate the secretion
of the hormone erythropoietin by the kidneys; this is a major
reason why men have a higher hematocrit than women.
Behavior
Androgens are essential in males for the development of sex
drive at puberty, and they play an important role in maintain-
ing sex drive (libido) in the adult male. A controversial question
is whether androgens infl uence other human behaviors in addi-
tion to sexual behavior. It has proven very diffi
cult to answer
this question with respect to human beings, but there is little
doubt that androgen-dependent behavioral differences based
on gender do exist in other mammals. For example, aggression
is clearly greater in male animals and is androgen-dependent.
Andropause
Changes in the male reproductive system with aging are less
drastic than those in women (described later in this chapter).
Once testosterone and pituitary gonadotropin secretions are
Table 17–3
Effects of Testosterone in the Male
1.
Required for initiation and maintenance of spermatogenesis
(acts via Sertoli cells)
2.
Decreases GnRH secretion via an action on the hypothalamus
3.
Inhibits LH secretion via a direct action on the anterior
pituitary
4.
Induces differentiation of male accessory reproductive
organs and maintains their function
5.
Induces male secondary sex characteristics; opposes action
of estrogen on breast growth
6.
Stimulates protein anabolism, bone growth, and cessation
of bone growth
7.
Required for sex drive and may enhance aggressive behavior
8.
Stimulates erythropoietin secretion by the kidneys
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