Chapter 11
The Endocrine Response to Stress
Much of this book is concerned with the body’s response to
in its broadest meaning as an environmental change
that must be adapted to if health and life are to be maintained.
Thus, any change in external temperature, water intake, or
other factor sets into motion mechanisms designed to prevent
a signifi cant change in some physiological variable. In this sec-
tion, the basic endocrine response to stress is described in the
sense of real or potential threats to homeostasis. These threats
comprise an immense number of situations, including physical
trauma, prolonged exposure to cold, prolonged heavy exercise,
infection, shock, decreased oxygen supply, sleep deprivation,
pain, fright, and other emotional stresses.
It is obvious that the response to cold exposure must be
very different from that to infection or fright, but in one respect
the response to all these situations is the same: Invariably, the
adrenal cortex’s secretion of the glucocorticoid hormone cor-
tisol is increased. Activity of the sympathetic nervous system,
including release of the hormone epinephrine from the adrenal
medulla, also usually increases in response to stress.
The increased cortisol secretion during stress is mediated
mainly by the hypothalamo-anterior pituitary system described
earlier. As previously illustrated in Figure 11–19, neural input
to the hypothalamus from portions of the nervous system
responding to a particular stress induces secretion of CRH.
This hormone is carried by the hypothalamo-pituitary portal
vessels to the anterior pituitary, where it stimulates ACTH
secretion. ACTH in turn circulates to the adrenal cortex and
stimulates cortisol release.
The secretion of ACTH, and therefore of cortisol, is
stimulated by several hormones in addition to hypothalamic
CRH. These include vasopressin, which usually increases in
response to stress. A most interesting recent fi nding is that
some of the cytokines (secretions from cells that comprise the
immune system; Chapter 18) also stimulate ACTH secretion
both directly and by stimulating the secretion of CRH. These
cytokines provide a means for eliciting an endocrine stress
response when the immune system is stimulated. The pos-
sible signifi
cance of this relationship for immune function is
described next and in Chapter 18.
Physiological Functions of Cortisol
Although the effects of cortisol are most dramatically illus-
trated during the response to stress, cortiso
l exerts many
important actions even in nonstress situations. For example,
cortisol has permissive actions on the reactivity to epineph-
rine and norepinephrine of muscle cells that surround blood
vessels. Thus, basal levels of cortisol are needed to maintain
normal blood pressure. Likewise, basal levels of cortisol are
required to maintain the cellular concentrations of certain
enzymes involved in metabolic homeostasis. These enzymes
are located primarily in the liver, and they act to increase
hepatic glucose production between meals, thus preventing
plasma glucose levels from decreasing below normal.
Two important systemic actions of cortisol are its anti-
infl ammatory and anti-immune functions. The mechanisms
by which cortisol inhibits immune system function are numer-
ous and complex. Cortisol inhibits the production of both leu-
kotrienes and prostaglandins, both of which are involved in
infl ammation. Cortisol also stabilizes lysosomal membranes
in damaged cells, preventing the release of their proteolytic
contents. In addition, cortisol reduces capillary permeability
in injured areas (thus, reducing fl uid leakage to the intersti-
tium), and it suppresses the growth and function of certain
key immune cells. Thus, cortisol may serve as a “brake” on the
immune system, which would tend to overreact to minor infec-
tions in the absence of cortisol. Indeed, in diseases in which
cortisol is greatly reduced, an increased incidence of autoim-
mune disease is sometimes noticed. Such diseases are charac-
terized by a person’s own immune system launching an attack
against part of the body.
During fetal and neonatal life, cortisol is also an extremely
important developmental hormone. It has been implicated
in the proper differentiation of numerous tissues and glands,
including various parts of the brain, the adrenal medulla, the
intestine and, notably, the lungs. In the latter case, cortisol is
very important for the production of surfactant, which reduces
surface tension in the lungs (see Chapter 13).
Thus, although it is common to defi ne the actions of cor-
tisol in the context of the stress response, it is worth remem-
bering that the maintenance of a homeostatic situation in the
absence of external stresses is also a critical function of cortisol.
Functions of Cortisol in Stress
Table 11–3
summarizes the major effects of increased cortisol
during stress. The effects on organic metabolism are to mobi-
lize fuels—to increase the plasma concentrations of amino
acids, glucose, glycerol, and free fatty acids. These effects are
ideally suited to meet a stressful situation. First, an animal
faced with a potential threat is usually forced to forego eating,
making these metabolic changes essential for survival during
fasting. Second, the amino acids liberated by catabolism of
body protein not only provide a source of glucose, via hepatic
gluconeogenesis, but also constitute a potential source of
amino acids for tissue repair should injury occur.
A few of the medically important implications of these
cortisol-induced effects on organic metabolism are as follows:
(1) any patient who is ill or is subjected to surgery catabolizes
considerable quantities of body protein; (2) a diabetic who
suffers an infection requires more insulin than usual; and (3)
a child subjected to severe stress of any kind may manifest
retarded growth.
Cortisol has important effects during stress other than
those on organic metabolism. It increases the ability of vascu-
lar smooth muscle to contract in response to norepinephrine.
Therefore, a patient with insuffi cient cortisol faced with even a
moderate stress, which usually releases unknown vasodilators,
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