Ganong's Review of Medical Physiology, 23rd Edition

400
SECTION IV
Endocrine & Reproductive Physiology

animals, precocious puberty can be produced by hypothalamic
lesions. Apparently the lesions interrupt a pathway that nor-
mally holds pulsatile GnRH secretion in check. Pineal tumors
are sometimes associated with precocious puberty, but evidence
indicates that these tumors are associated with precocity only
when there is secondary damage to the hypothalamus.
Precocious gametogenesis and steroidogenesis can occur
without the pubertal pattern of gonadotropin secretion (gonad-
otropin-independent precocity). At least in some cases of this
condition, the sensitivity of LH receptors to gonadotropins is
increased because of an activating mutation in the G protein
that couples the receptors to adenylyl cyclase.

Delayed or Absent Puberty

The normal variation in the age at which adolescent changes oc-
cur is so wide that puberty cannot be considered to be patholog-
ically delayed until the menarche has failed to occur by the age
of 17 or testicular development by the age of 20. Failure of mat-
uration due to panhypopituitarism is associated with dwarfing
and evidence of other endocrine abnormalities. Patients with
the XO chromosomal pattern and gonadal dysgenesis are also
dwarfed. In some individuals, puberty is delayed even though
the gonads are present and other endocrine functions are nor-
mal. In males, this clinical picture is called
eunuchoidism.
In
females, it is called
primary amenorrhea.

MENOPAUSE

The human ovaries become unresponsive to gonadotropins
with advancing age, and their function declines, so that sexual
cycles disappear
(menopause).
This unresponsiveness is asso-
ciated with and probably caused by a decline in the number of
primordial follicles, which becomes precipitous at the time of
menopause (Figure 25–10). The ovaries no longer secrete
progesterone and 17
β
-estradiol in appreciable quantities, and
estrogen is formed only in small amounts by aromatization of
androstenedione in peripheral tissues (see Chapter 22). The
uterus and the vagina gradually become atrophic. As the neg-
ative feedback effect of estrogens and progesterone is reduced,
secretion of FSH is increased, and plasma FSH increases to
high levels, LH levels are moderately high. Old female mice
and rats have long periods of diestrus and increased levels of
gonadotropin secretion. In women, a period called perimeno-
pause precedes menopause, and can last up to 10 y. During
perimenopause the menses become irregular and the level of
inhibins decrease, usually between the ages of 45 and 55. The
average age at onset of the menopause has been increasing
since the end of the 19th century and is currently 52 y.
The loss of ovarian function causes many symptoms such as
sensations of warmth spreading from the trunk to the face
(hot flushes; also called hot flashes) and night sweats. In addi-
tion, the onset of menopause increases the risk of many dis-
eases such as osteoporosis, ischemic heart disease, and renal
disease.

Hot flushes are said to occur in 75% of menopausal women

and may continue intermittently for as long as 40 y. They also

occur when early menopause is produced by bilateral ovariec-

tomy, and they are prevented by estrogen treatment. In addi-

tion, they occur after castration in men. Their cause is

unknown. However, they coincide with surges of LH secre-

tion. LH is secreted in episodic bursts at intervals of 30 to 60

min or more

(circhoral secretion),

and in the absence of

gonadal hormones these bursts are large. Each hot flush

begins with the start of a burst. However, LH itself is not

responsible for the symptoms, because they can continue after

removal of the pituitary. Instead, it appears that some estro-

gen-sensitive event in the hypothalamus initiates both the

release of LH and the episode of flushing.

Although the function of the testes tends to decline slowly

with advancing age, the evidence is unclear whether there is a

“male menopause”

(andropause)

similar to that occurring in

women.

PITUITARY GONADOTROPINS

& PROLACTIN

CHEMISTRY

FSH and LH are each made up of an

α

and a

β

subunit whose

nature is discussed in Chapter 24. They are glycoproteins that

contain the hexoses mannose and galactose, the hexosamines

N

-acetylgalactosamine and

N-

acetylglycosamine, and the

methylpentose fucose. They also contain sialic acid. The car-

bohydrate in the gonadotropin molecules increases their

FIGURE 25–10

Number of primordial follicles per ovary in

women at various ages.

Blue squares, premenopausal women (regu-

lar menses); red squares, perimenopausal women (irregular menses

for at least 1 y); red triangles, postmenopausal women (no menses for

at least 1 y). Note that the vertical scale is a log scale and that the values

are from one rather than two ovaries.

(Redrawn by PM Wise and reproduced

with permission from Richardson SJ, Senikas V, Nelson JF: Follicular depletion during

the menopausal transition: Evidence for accelerated loss and ultimate exhaustion.

J Clin Endocrinol Metab 1987;65:1231.)

100,000

10,000

1000

100

10

1

0

10 20 30 40 50 60

Age in years

Primordial follicles/ovary