Ganong's Review of Medical Physiology, 23rd Edition

408 SECTION IVEndocrine & Reproductive Physiology

Chapter 15. Although body hair is increased by androgens,
scalp hair is decreased (Figure 25–17). Hereditary baldness of-
ten fails to develop unless dihydrotestosterone is present.

Anabolic Effects

Androgens increase the synthesis and decrease the breakdown
of protein, leading to an increase in the rate of growth. It used to
be argued that they cause the epiphyses to fuse to the long
bones, thus eventually stopping growth, but it now appears that
epiphysial closure is due to estrogens (see Chapter 23). Second-
ary to their anabolic effects, androgens cause moderate Na+, K+,
H 2 O, Ca2+, SO 4 – , and PO 4 – retention; and they also increase the
size of the kidneys. Doses of exogenous testosterone that exert
significant anabolic effects are also masculinizing and increase
libido, which limits the usefulness of the hormone as an anabol-
ic agent in patients with wasting diseases. Attempts to develop
synthetic steroids in which the anabolic action is divorced from
the androgenic action have not been successful.

Mechanism of Action

Like other steroids, testosterone binds to an intracellular re-

ceptor, and the receptor–steroid complex then binds to DNA

in the nucleus, facilitating transcription of various genes. In

addition, testosterone is converted to dihydrotestosterone

(DHT) by 5α-reductase in some target cells (Figures 25–15

and 25–18), and DHT binds to the same intracellular receptor

as testosterone. DHT also circulates, with a plasma level that is

about 10% of the testosterone level. Testosterone–receptor

complexes are less stable than DHT–receptor complexes in

target cells, and they conform less well to the DNA-binding

state. Thus, DHT formation is a way of amplifying the action of

testosterone in target tissues. Humans have two 5α-reductases,

encoded by different genes. Type 1 5α-reductase is present in

skin throughout the body and is the dominant enzyme in the

scalp. Type 2 5α-reductase is present in genital skin, the pros-

tate, and other genital tissues.

Testosterone–receptor complexes are responsible for the

maturation of wolffian duct structures and consequently for

the formation of male internal genitalia during development,

but DHT–receptor complexes are needed to form male exter-

nal genitalia (Figure 25–18). DHT–receptor complexes are

FIGURE 25–17 Hairline in children and adults. The hairline of the woman is like that of the child, whereas that of the man is indented in
the lateral frontal region.

FIGURE 25–18 Schematic diagram of the actions of testosterone (solid arrows) and dihydrotestosterone (dashed arrows).
Note that they both bind to the same receptor, but DHT binds more effectively. (Reproduced with permission from Wilson JD, Griffin JE, Russell W: Steroid
5 α-reductase 2 deficiency. Endocr Rev 1993;14:577. Copyright © 1993 by The Endocrine Society.)

Testosterone

Testis

5 α-

Reductase

Dihydrotestosterone

Receptor

Gonadotropin

regulation

Spermato-

genesis

Sexual

maturation

at puberty

Sexual

differentiation

Wolffian

stimulation

External

virilization

Luteinizing

hormone

Target

cell