The Endocrine System
349
cifi cally, for normal maturation of the fetal nervous system. The
stimulus for IGF-1 secretion during prenatal life is unknown.
Finally
, it should be noted that there is another
messenger—
insulin-like growth factor 2 (IGF-2)
—that is
closely related to IGF-1. IGF-2, the secretion of which is
inde-
pendent
of growth hormone, is also a crucial mitogen during
the prenatal period. It continues to be secreted throughout
life, but its postnatal function is not known.
Thyroid Hormones
Thyroid hormones are essential for normal growth because
they are required for both the synthesis and the growth-
promoting effects of growth hormone. Thus, infants and
children with hypothyroidism manifest retarded growth due
to slowed bone growth.
Insulin
The major actions of insulin are described in Chapter 16. Insulin
is an anabolic hormone that promotes the entry of glucose and
amino acids from the extracellular fl uid into cells. Insulin stim-
ulates storage of fat and inhibits protein degradation. Thus, it
is not surprising that adequate amounts of insulin are necessary
for normal growth. Its inhibitory effect on protein degradation
is particularly important with regard to growth.
In addition to this general anabolic effect, however,
insulin exerts direct growth-promoting effects on cell differ-
entiation and cell division during fetal life, and possibly dur-
ing childhood.
Sex Hormones
As Chapter 17 will explain, sex hormone secretion (testoster-
one in the male and estrogens in the female) begins to increase
between the ages of 8 and 10 and reaches a plateau over the
next 5 to 10 years. A normal pubertal growth spurt, which
refl ects growth of the long bones and vertebrae, requires this
increased production of the sex hormones. The major growth-
promoting effect of the sex hormones is to stimulate the secre-
tion of growth hormone and IGF-1.
Unlike growth hormone, however, the sex hormones not
only stimulate bone growth, but ultimately
stop
it by induc-
ing epiphyseal closure. The dual effects of the sex hormones
explain the pattern seen in adolescence—rapid lengthening of
the bones culminating in complete cessation of growth for life.
In addition to these dual effects on bone, testosterone,
but not estrogen, exerts a direct anabolic effect on protein
synthesis in many nonreproductive organs and tissues of the
body. This accounts, at least in part, for the increased muscle
mass of men in comparison to women.
This effect of testosterone is also why athletes some-
times use androgens called
anabolic steroids
in an attempt
to increase muscle mass and strength. These steroids include
Figure 11–28
Hormonal pathways controlling the secretion of growth
hormone (GH) and insulin-like growth factor I (IGF-1). At the
hypothalamus, the minus sign
E
denotes that the input inhibits
the secretion of growth hormone–releasing hormone (GHRH)
and/or stimulates the release of somatostatin (SS). Which of these
mechanisms predominates in humans is currently unknown. Not
shown in the fi gure is that several hormones not in the sequence
(e.g., the thyroid hormones) infl uence growth hormone secretion
via effects on the hypothalamus and/or anterior pituitary.
Begin
Plasma IGF-1
Plasma GH
and/or
(in hypothalamo-pituitary portal vessels)
Plasma SS
Plasma GHRH
SS secretion
GHRH secretion
Stimulus:
Exercise, stress, fasting, low plasma glucose, sleep
Liver and other cells
IGF-1 secretion
Anterior pituitary
GH secretion
Hypothalamus
and/or
Short-loop feedb
a
ck
Long-loop feedb
a
ck
administration of GH to an otherwise healthy individual (such
as an athlete) can lead to serious side-effects. Abuse of GH in
such situations can lead to symptoms similar to those of diabetes
mellitus, as well as numerous other problems. The consequences
of chronically elevated growth hormone levels are dramati-
cally illustrated in the disease called acromegaly (see Additional
Clinical Examples at the end of this section).
As noted, growth hormone plays little if any role in the
growth of the embryo and fetus. One would suppose, therefore,
that this would also be true for IGF-1, but this is not the case.
IGF-1 is required for normal fetal total-body growth and, spe-
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