714 Chapter 20by the conversion of testosterone to estradiol by aromatase
within certain brain neurons. In male mice, this estradiol effect
is needed for later development of male sexual behavior, ter-
ritoriality, and aggression.
DHT is produced by the action of 5 a -reductase in the cells
of the prostate and skin, and is the molecule responsible for the
androgenic stimulation of those organs. Estradiol, formed from
testosterone by the action of aromatase in osteocytes, stimulates
the skeletal system of males (chapter 19, section 19.6). Recent
evidence supports the role of androgens in stimulating muscle
size and strength, but of estrogen (derived from testosterone in
adipocytes) in the regulation of adipose tissue in males. Both
testosterone and estradiol are required for male sexual function.Testosterone Secretion and Age
The negative feedback effects of testosterone and inhibin help
to maintain a relatively constant (that is, noncyclic) secretion of
gonadotropins in males, resulting in relatively constant levels
of androgen secretion from the testes. This contrasts with the
cyclic secretion of gonadotropins and ovarian steroids in females.
Women experience an abrupt cessation in sex steroid secre-
tion during menopause. By contrast, the secretion of androgens
declines only gradually and to varying degrees in men. The causes
of this age-related change in testicular function are not currently
known. The decline in testosterone secretion cannot be due to
decreasing gonadotropin secretion, since gonadotropin levels in
the blood are, in fact, elevated (because of less negative feedback)
at the time that testosterone levels are declining.
Testosterone levels decline slowly in men past their 20s,
commonly reaching a hypogonadal state (defined as plasma tes-
tosterone concentrations below 320 ng/dl) by age 70. Besides
age, additional factors that lower plasma testosterone levels are
physical inactivity, obesity, and drugs. Low testosterone levels
are associated with a reduction in lean muscle and bone mass.Endocrine Functions of the Testes
Testosterone is by far the major androgen secreted by the
adult testis. This hormone and its derivatives (the 5 a -reduced
androgens) are responsible for initiation and maintenance of
the body changes associated with puberty in males. Androgens
are sometimes called anabolic steroids because they stimulate
anabolism (synthesis reactions; chapter 19, section 19.1) lead-
ing to the growth of muscles and other structures ( table 20.4 ).
Increased testosterone secretion during puberty is also required
for growth of the accessory sex organs—primarily the semi-
nal vesicles and prostate. Removal of androgens by castration
results in atrophy of these organs.
Androgens stimulate growth of the larynx (causing a low-
ering of the voice) and promote hemoglobin synthesis (males
have higher hemoglobin levels than females) and bone growth.
The effect of androgens on bone growth is self-limiting, how-
ever, because they ultimately cause replacement of cartilage
by bone in the epiphyseal discs, thus “sealing” the discs and
preventing further lengthening of the bones.Figure 20.13 Derivatives of testosterone.
Testosterone secreted by the interstitial (Leydig) cells of the
testes can be converted into active metabolites in the brain and
other target organs. These active metabolites include DHT and
other 5 a -reduced androgens and estradiol.HO HO
HOOHOHOHOHOH5 α-Androstane-
3 β,17β-diol
(3훃-diol)5 α-Androstane-
3 α,17β-diol
(3훂-diol)5 훂-DHTAromataseEstradiol-17훃Testosterone
5 α-ReductaseOOof the human testes also have been shown to produce inhibin,
which inhibits FSH secretion in men. (There is also evidence
that inhibin is produced by the ovaries, where it may function
as a hormone and as a paracrine regulator of the ovaries.)Testosterone Derivatives
The brain contains testosterone receptors and is a target organ
for this hormone. The effects of testosterone on the brain, such
as the suppression of LH secretion, are not mediated directly
by testosterone, however, but rather by its derivatives that are
produced within the brain cells. Testosterone may be converted
by the enzyme 5 a -reductase to dihydrotestosterone (DHT),
as previously described. The DHT, in turn, can be changed by
other enzymes into other 5 a -reduced androgens—abbreviated
3 a -diol and 3 b -diol ( fig. 20.13 ). Alternatively, testosterone may
be converted within the brain to estradiol-17 b. Although usually
regarded as a female sex steroid, estradiol is therefore an active
compound in normal male physiology. Estradiol is formed from
testosterone by the action of an enzyme called aromatase. This
reaction is known as aromatization, a term that refers to the pres-
ence of an aromatic carbon ring (chapter 2, section 2.1). The
estradiol formed from testosterone in the brain is required for the
negative feedback effects of testosterone on LH secretion.
There are some differences between the brains of male
and female mammals that are established during fetal develop-
ment and result from testosterone released from the fetal testes.
Some of these differences are caused by testosterone binding
to its androgen receptors in brain cells, but others are caused