The Endocrine System
339
Metabolic Actions
Thyroid hormones have several effects on carbohydrate and lipid
metabolism, although not to the extent as other hormones such
as insulin. Nonetheless, TH stimulates carbohydrate absorption
from the small intestine and increases fatty acid release from adi-
pocytes. These actions provide energy to maintain metabolic rate
at a high level, and are consistent with one of the major actions
of TH, which is to stimulate the activity of Na
+
/K
+
-ATPases
throughout the body. Recall from Chapter 3 that ATP nega-
tively feeds back on glycolytic enzymes within cells to maintain
its cellular concentration. A decrease in cellular stores of ATP
therefore triggers an increase in glycolysis, which results in the
burning of additional fuel to restore ATP levels. One of the by-
products of this process is heat. Thus, as ATP is consumed by
Na
+
/K
+
-ATPases at a high rate due to TH activation, the cellular
stores of ATP must be maintained by increased metabolism of
fuels. This
calorigenic
action of TH represents a very signifi cant
fraction of the total heat produced each day in a typical person.
Permissive Actions
Many of the actions of TH are attributable to its permissive
effects on catecholamines. TH up-regulates beta-adrenergic
receptors in many tissues, notably the heart and nervous sys-
tem. Thus, it should not be surprising that the symptoms of
excess thyroid hormone concentration closely resemble some
of the symptoms of excess epinephrine and norepinephrine
(sympathetic nervous system activity). That is because the
increased thyroid hormone potentiates the actions of the cat-
echolamines, even though the latter are within normal levels.
Because of this potentiating effect, people with hyperthyroid-
ism are often treated with drugs that block beta-adrenergic
receptors to alleviate the anxiety, nervousness, and “racing
heart” associated with excessive sympathetic activity.
Growth and Development
As described in Section E of this chapter, TH is needed for
normal production of growth hormone. Therefore, in the
absence of TH, growth in children is decreased. In addi-
tion, though, TH is among the most important developmen-
tal hormones for the nervous system. During fetal life, TH
exerts many effects on central nervous system development,
including the formation of nerve terminals and the pro-
duction of synapses, the growth of dendrites and dendritic
extensions (called “spines”), and the formation of myelin.
Absence of TH during fetal life results in a poorly devel-
oped nervous system and a form of mental retardation called
cretinism
.
The most common cause of cretinism around
the world (but rare in the United States) is dietary iodine
defi ciency in the mother. Without iodine in her diet, little
iodine is made available to the fetus. Thus, even though the
fetal thyroid may be normal, it cannot manufacture suffi
cient
TH. If the condition is discovered and corrected with iodine
and TH administration shortly after birth, mental and physi-
cal retardation can be prevented. Some evidence suggests,
however, that completely normal mental function may not be
restored. Furthermore, if the treatment is not initiated in the
early neonatal period, cretinism cannot be reversed. Despite
the availability of iodized salt products in many countries,
cretinism is still a common disorder in some parts of the
world, particularly in mountainous regions where snow and
rainwater leach iodine out of the soil.
The effects of TH on nervous system function are not
limited to fetal and neonatal life. For example, TH is needed
for proper nerve/muscle refl exes and for normal cognition in
adults.
Target cells for thyroid hormone
T
4
converted to T
3
Respond to increased T
3
Plasma thyroid hormone
Thyroid gland
Thyroid hormone (T
3
, T
4
) secretion
Plasma TSH
Anterior pituitary
TSH secretion
Plasma TRH
(in hypothalamo-pituitary portal vessels)
Hypothalamus
TRH secretion
Neural inputs
Begin
Figure 11–23
TRH-TSH-thyroid hormone sequence. T
3
and T
4
inhibit secretion
of TSH and TRH by negative feedback, indicated by the
E
symbol.
previous page 367 Vander's Human Physiology The Mechanisms of Body Function read online next page 369 Vander's Human Physiology The Mechanisms of Body Function read online Home Toggle text on/off