Reproductive (Androgenic) Effects
Testes (Spermatogenesis)
At puberty, locally produced
testosterone promotes spermatogenesis in the seminif-
erous tubules, although it is not known with certainty
whether or not the Sertoli cells contain 5a-reductase. As
mentioned above, testosterone alone promotes the two
meiotic (maturational) divisions if present in high con-
centrations within the tubule, but it is not capable of ini-
tiating spermatogenesis in the absence of FSH. Thus, in
cases of drug-induced azoospermia, FSH (not androgens)
is required for reinitiation of spermatogenesis.
Internal and External Genitalia
In the fetus, testos-
terone causes differentiation of the Wolffian ducts into the
male-type reproductive tract, and thereby rescues the tis-
sue from pre-programmed destruction. The seminal vesi-
cles, which differentiate from the Wolffian duct as a result
of testosterone action, produce 5a-reductase-2 from week
13-14 and becomes DHT-responsive after that; thus, de-
velopment and function (but not appearance) may be reg-
ulated by DHT from the second trimester through adult-
hood. On the other hand, the urogenital sinus and external
genital primordium in the fetus contain 5a-reductase-2
before week
and require DHT for their differentiation
into the male phenotype. These tissues do not respond
to the very high levels of testosterone in fetal plasma
during the critical period (weeks
1 2
) unless they are
able to convert it into DHT. This explains why
5a-reductase deficiency
in genotypic male fetuses results
in the development of female-type external genitalia, de-
spite the normal production of testosterone by the fetal
testes. At puberty, however, the derivative of the genital
tubercle (clitoris and penis) becomes responsive to testos-
terone, which enhances the male-type morphology by pro-
moting growth of the existing structure. On the other hand,
the growth and initiation of function of the prostate (uro-
genital sinus derivative) from puberty through adulthood
requires DHT, and testosterone alone does not substitute.
The importance of DHT in prostate growth and function is
underscored by the success with which
benign prostatic
(BPH) in adults can be controlled by blocking
5a-reductase activity.
The hair follicles and sebaceous glands (col-
lectively called pilosebaceous units) in the androgen-
sensitive areas of the skin and sebaceous glands throughout
the body contain 5a-reductase type 1 and respond to DHT.
At puberty, DHT stimulates the appearance and growth
of terminal hair in certain androgen-sensitive regions of
the body (face, chest, upper pubic triangle, nostrils, ex-
any steroid that can activate the AR will evoke both an-
drogenic and anabolic responses.
temal ear). Testicular testosterone in boys and adrenal an-
drostenedione in girls stimulate the appearance and growth
of terminal hair in the axillae and lower pubis, presumably
after conversion to DHT in the hair follicles in these re-
gions. Axillary and lower pubic hair growth requires less
androgen than that in the face, chest, upper pubic area,
nose, and ear; thus, hair in
mons pubis
is the most sensi-
tive to androgen (i.e., responds to lower amounts), beard
is least sensitive (i.e., requires higher amounts).
DHT stimulates the growth and secretory function (se-
bum production) of all sebaceous glands, and thus pre-
disposes the skin to acne formation, This DHT-promoted
effect can be reversed or attenuated by treatment with es-
trogens, which antagonize the actions of DHT on the seba-
ceous glands and cause a depression in glandular activity.
In adulthood, the changes at puberty are maintained by
the same hormones, but in many men and few women
varying degrees of hairline recession occur as a result of
sex-linked genetic predisposition and a DHT effect. Hair
on the frontal and vertex scalp is converted from termi-
nal to vellus types in response to DHT (the opposite of
what occurs in other androgen-sensitive areas), resulting
in the “male pattern baldness”; in women, this is one of
the signs of hirsutism. A reduction in circulating testos-
terone and/or inhibition of 5a-reductase activity (e.g., with
finasteride) will prevent or retard the terminal-to-vellus
Voice Pitch
Testosterone promotes enlargement of the
larynx and thickening of the vocal folds (vocal cords),
causing a lowering of the voice pitch. The larynx and as-
sociated vocal fold mucosa do not contain 5a-reductase;
thus, deepening of the voice occurs at puberty in boys
due to the increased production of testosterone, and this is
seen even in hereditary 5a-reductase deficiency. Once es-
tablished at puberty, the laryngeal vocal structures do not
require significant amounts of androgens for maintenance;
in fact, bilateral testicular failure or loss in a previously
normal adult male may not result in any change in voice
pitch, possibly because of the adequacy of androgens from
the adrenals.
Nonreproductive Effects
Skeletal Muscle
Skeletal muscle has no 5a-reductase, and,
although all skeletal muscles are believed to contain AR,
some are known to contain a higher concentration than
others. The most androgen-responsive skeletal muscle in
man (presumably because of a higher concentration of
AR) are those of the pectoral and shoulder regions. In
other species (e.g., rodents), testosterone promotes skele-
tal muscle growth by stimulating both hypertrophy and
mitosis of myofibrils and increases the fast-twitch isoform
previous page 820 Bhagavan Medical Biochemistry 2001 read online next page 822 Bhagavan Medical Biochemistry 2001 read online Home Toggle text on/off