with
camptomelic dysplasia.
The latter is a severe form
of skeletal dysplasia associated with dysmorphic features
and cardiac defects.
After the fetal gonads are converted into testes by
SRY,
testosterone and Mullerian-inhibiting substance (MIS)
control subsequent sexual differentiation. MIS causes the
regression of the Mullerian duct, which would otherwise
develop into female genital tracts. Testosterone promotes
the development of the Wolffian duct into male internal
genitalia, including epididymis, vas deferens, and seminal
vesicles.
Testosterone also causes differentiation of the urogen-
ital sinus into the prostate gland and masculinizes the
external genitalia; however, these tissues must first con-
vert testosterone into dihydrotestosterone (DHT), a reac-
tion catalyzed by cytoplasmic 5a-reductase type 2. The
effects of testosterone on the Wolffian duct and urogenital
sinus are dependent on the presence of androgen recep-
tors and 5a-reductase, which are expressed by genes on
the X chromosome and chromosome 2, respectively, and
are present in both genotypic sexes. This explains why ex-
posure of the fetus to androgens during the critical period
may lead to masculinization of the internal and external
genitalia of genotypic female fetuses. It also explains why
lack of expression of either gene can lead to feminization
in genotypic male fetuses.
The gonad has two interrelated functions: gameto-
genesis and hormone production. Gametogenesis de-
pends on gonadal hormone production, which is influ-
enced by gametogenesis. Both processes are controlled
by luteinizing hormone (LH) and follical-stimulating hor-
mone (FSH), which are released in response to hy-
pothalmic gonadotropin-releasing hormone (GnRH) and
to the levels of circulating gonadal hormones. In addition,
gametogenesis is regulated by paracrine actions of the go-
nadal hormones.
The obvious difference between the sexes in gameto-
genesis is formation of ova (ootids) in the female and
of sperm (spermatozoa) in the male. Spermatogenesis
becomes operational from about the time of puberty and
continues throughout life. The process takes about 74
days. Oogenesis occurs in three phases. The initial phase
involves proliferation of the stem cells (oogonia) and oc-
curs only in fetal life. The second phase involves the first
maturational division (formation of the secondary oocyte)
and occurs about the time of ovulation (see below). The
third phase involves the second and final maturational
division (formation of ova) and occurs at fertilization.
Because the number of oogonia is determined before
birth, the number of fertilizable ova that can be produced
in a woman’s lifetime is limited and is greatly reduced
by normal degenerative processes (atresia), so that of
the estimated seven million oogonia in the fetal ovaries,
782
only about 300-500 ova ultimately develop. Unlike the
continuous generation of sperm in the testes, the ovaries
generally produce only one secondary oocyte every
22-28 days. The fertile lifetime in the average woman is
about 35-40 years. Ovaries and testes produce identical
steroid hormones, but the amounts and their patterns of
secretion are different (Table 34-1). Although testosterone
is present in both males and females, its level in the
male is about 18 times that in the female; conversely,
circulating levels of estradiol in the female are about 3-15
times those in the male. In either sex, the major sex steroid
originates in the gonads, whereas in the opposite sex, this
steroid is generated in sustantial amounts by the adrenal
cortex or by peripheral conversion of another steroid.
For example, almost all of the circulating estradiol in
the female comes from the ovaries, whereas in the male,
only about one-third comes from the tests, the rest being
generated by peripheral conversion of androgenic precur-
sors. Finally, the pattern of gonadal steroid secretion is
different. In the male, the secretion of gonadal steroids
is fairly constant, although minor fluctuations occur as a
result of circadian rhythms. In the adult female, gonadal
steroid secretion undergoes dramatic, cyclic changes at
about monthly intervals. These cyclic changes, which are
dictated by processes regulating oogenesis, are referred
to as the menstrual cycle.
chapter
34
Endocrine Metabolism V: Reproductive System
34.1 Testes
Regulation of Spermatogenesis:
Sertoli-Neuroendocrine Axis
Sertoli cells are epithelial cells that line the seminiferous
tubules of the testes. At their basal aspects, these cells form
the basement membrane and tight junctions that make up
the highly selective “blood-testes barrier,” which normally
prevents entry of immune cells into the lumen.
Their function is to provide nutritional and hormonal
support for cells undergoing spermatogenic transforma-
tion (i.e., spermatocytes and spermatids). For this rea-
son, they are often referred to as “nurse cells.” Sertoli
cells require FSH stimulation for their maintenance and
specifically for production of
androgen-binding protein
(ABP). ABP, which has a high affinity for testosterone,
maintains high levels of testosterone in the seminiferous
tubules and thereby helps maintain spermatogenesis. FSH
also stimulates aromatase activity in the Sertoli cell, thus
stimulating conversion of testosterone into estradiol. This
FSH-sensitive Sertoli cell activity accounts for most of the
testicular output of estradiol.
FSH secretion by the anterior pituitary is held in check
by negative feedback from the testes. This feedback is
