Human Physiology, 14th edition (2016)

Reproduction 715

ability to produce estrogen or who lack estrogen receptors (due

to rare genetic defects only recently discovered) maintain their

epiphyseal plates and continue to grow.

The two compartments of the testes interact with each other in

paracrine fashion ( fig. 20.14 ). Paracrine regulation refers to chemi-

cal regulation that occurs among tissues within an organ (chapter 11,

section 11.7). Testosterone from the Leydig cells is metabolized

by the tubules into other active androgens and is required for

spermatogenesis, for example. The tubules also secrete paracrine

regulators that may influence Leydig cell function.

Inhibin secreted by the Sertoli cells in response to FSH can

facilitate the Leydig cells’ response to LH, as measured by the

amount of testosterone secreted. Further, it has been shown that

the Leydig cells are capable of producing a family of polypep-

tides previously associated with the pituitary gland and brain—

ACTH, MSH, and b -endorphin. Experiments suggest that

ACTH and MSH can stimulate Sertoli cell function, whereas

b -endorphin can inhibit Sertoli function. The physiological sig-

nificance of these fascinating paracrine interactions between

the two compartments of the testes remains to be demonstrated.

Spermatogenesis

The germ cells that migrate from the yolk sac to the testes

during early embryonic development become spermatogenic

stem cells, called spermatogonia. The stem cell spermato-

gonia are located in the outermost region of the seminiferous

tubules, right against the basement membrane (basal lamina),

so that they are as close as they can be to the blood vessels

in the interstitial tissue. Spermatogonia are diploid cells (with

Although androgens are by far the major endocrine products
of the testes, there is evidence that Sertoli cells, Leydig cells,
and developing sperm cells secrete estradiol. Further, receptors
for estradiol are found in Sertoli and Leydig cells, as well as in
the cells lining the male reproductive tract (efferent ductules and
epididymis) and accessory sex organs (prostate and seminal ves-
icles). Estrogen receptors have also been located in the develop-
ing sperm cells (spermatocytes and spermatids, described in the
next section) of many species, including humans. This suggests
a role for estrogens in spermatogenesis, and indeed knockout
mice (chapter 3) missing an estrogen receptor gene are infertile.
Further, men with a congenital deficiency in aromatase—the
enzyme that converts androgens to estrogens ( fig.  20.13 )—are
also infertile.
The developing sperm cells contain aromatase for the pro-
duction of estrogen ( fig. 20.13 ), suggesting that they may regu-
late their environment by means of this hormone. Even mature
sperm that travel through the rete testis and efferent ductules
(see fig. 20.11 ) can produce estradiol, although their ability to
do this is abolished by the time they get to the tail of the epi-
didymis. Since the efferent ductules are rich in estrogen recep-
tors, the estrogen delivered to them by the sperm in the lumen
may help regulate their functions, including fluid reabsorption.
Estradiol produced locally as a paracrine regulator may be
responsible for a number of effects in men that have previously
been attributed to androgens. For example, the importance of
the conversion of testosterone into estradiol in the brain for
negative feedback control was described earlier. Estrogen also
may be responsible for sealing of the epiphyseal plates of car-
tilage; this is suggested by observations that men who lack the

Table 20.4 | Actions of Androgens
in the Male

Category Action

Sex Determination Growth and development of wolffian ducts

into epididymis, ductus deferens,

seminal vesicles, and ejaculatory ducts

Development of urogenital sinus into prostate

Development of male external genitalia

(penis and scrotum)

Spermatogenesis At puberty: Completion of meiotic division

and early maturation of spermatids

After puberty: Maintenance of

spermatogenesis

Secondary Sex

Characteristics

Growth and maintenance of accessory

sex organs

Growth of penis

Growth of facial and axillary hair

Body growth

Anabolic Effects Protein synthesis and muscle growth

Growth of bones

Growth of other organs (including larynx)

Erythropoiesis (red blood cell formation)

Figure 20.14 Interactions between the two

compartments of the testes. Testosterone secreted by

the interstitial (Leydig) cells stimulates spermatogenesis in

the tubules. Leydig cells may also secrete ACTH, MSH, and

b -endorphin. Secretion of inhibin by the tubules may affect the

sensitivity of the Leydig cells to LH stimulation.

FSH LH

Testosterone

5 α-reduced

androgens

Estradiol

Inhibin

Seminiferous

tubules

Interstitial

(Leydig) cells

Spermatogenesis

Anterior pituitary

(?)

Polypeptides

(ACTH, MSH, β-endorphin)

(?)