C h a p t e r 9
Stress and Adaptation
209
Neuroendocrine Responses
The stress response is mediated by anatomical structures
found in both the central nervous system and peripheral
tissues. Manifestations of the stress response are strongly
influenced by both the nervous and endocrine sys-
tems.
9,16,17
The neuroendocrine systems integrate signals
received along neurosensory pathways and from circulat-
ing mediators that are carried in the bloodstream. In addi-
tion, the immune system both affects and is affected by the
stress response. Table 9-1 summarizes the action of hor-
mones involved in the neuroendocrine responses to stress.
Results of the coordinated release of these neurohor-
mones include mobilization of energy, a sharpened focus
and awareness, increased cerebral blood flow and glu-
cose utilization, enhanced cardiovascular and respiratory
functioning, redistribution of blood flow to the brain and
muscles, modulation of the immune response, inhibition
of reproductive function, and a decrease in appetite.
16,17
The stress response is a normal, coordinated physiologic
system intended to increase the probability of survival, but
importantly, it also is designed to be an acute response.
That is, optimally it is turned on when necessary to bring
the body back to a stable state and turned off when the
challenge to homeostasis abates. Therefore, under normal
circumstances, the neural responses and hormones that are
released during the response do not persist long enough to
cause damage to vital tissues. Since the early 1980s, the
term
allostasis
has been used by some investigators to
describe the interactive physiologic changes in the neuro-
endocrine, autonomic, and immune systems that occur in
response to either real or perceived challenges to homeo-
stasis. More recently, others have proposed that allosta-
sis is the body’s attempt to maintain stability through
change, thereby adequately or inadequately adapting to
threatening or unpredictable stimuli.
18
The persistence or
accumulation of these allostatic changes (e.g., immuno-
suppression, activation of the sympathetic nervous and
renin-angiotensin-aldosterone systems) has been called an
allostatic load,
and this concept has been used to measure
the cumulative effects of stress on humans.
16–21
Allostatic
load can result in weakening a person’s ability to respond
to repeated stressors, and it may provide insight into how
one might respond to future stressors. A number of indices
have been suggested for measuring allostatic load, includ-
ing blood pressure, cortisol, C-reactive protein, body mass
index (BMI), and cholesterol.
22
Integration of the components of the stress response,
occurring at the level of the central nervous system
(CNS), is complex and not completely understood.
23,24
It relies on communication along neuronal pathways
of the cerebral cortex, limbic system, thalamus, hypo-
thalamus, pituitary gland, and reticular activating sys-
tem (RAS). The cerebral cortex is involved in vigilance,
cognition, and focused attention, while the limbic sys-
tem is associated with emotional components (e.g., fear,
excitement, rage, anger) of the stress response (Fig. 9-2).
The thalamus functions as the relay center and is impor-
tant in receiving, sorting out, and distributing sensory
input. The hypothalamus coordinates responses of the
endocrine system and autonomic nervous system (ANS).
The RAS modulates mental alertness, ANS activity, and
skeletal muscle tone using input from other neural struc-
tures. The musculoskeletal tension that occurs during
the stress response reflects increased activity of the RAS
and its influence on reflex circuits that control muscle
tone. Adding to the complexity of this system is the fact
that individual brain circuits that participate in media-
tion of the stress response interact and regulate each
other’s activities. For example, reciprocal connections
TABLE 9-1
Hormones Involved in the Neuroendocrine Responses to Stress
Hormones Associated with the
Stress Response
Source of the
Hormone
Physiologic Effects
Catecholamines (norepinephrine,
epinephrine)
Locus ceruleus, adrenal
medulla
Produces a decrease in insulin release and an increase in
glucagon release resulting in increased glycogenolysis,
gluconeogenesis, lipolysis, proteolysis, and decreased
glucose uptake by the peripheral tissues; an increase
in heart rate, cardiac contractility, and vascular smooth
muscle contraction; and relaxation of bronchial smooth
muscle
Corticotropin-releasing factor (CRF)
Hypothalamus
Stimulates ACTH release from anterior pituitary and
increased activity of neurons in locus ceruleus
Adrenocorticotropic hormone (ACTH)
Anterior pituitary
Stimulates the synthesis and release of cortisol
Glucocorticoid hormones (e.g., cortisol)
Adrenal cortex
Potentiates the actions of epinephrine and glucagon;
inhibits the release and/or actions of the reproductive
hormones and thyroid-stimulating hormone; and
produces a decrease in immune cells and inflammatory
mediators
Mineralocorticoid hormones (e.g.,
aldosterone)
Adrenal cortex
Increases sodium absorption by the kidney
Antidiuretic hormone (ADH,
vasopressin)
Hypothalamus,
posterior pituitary
Increases water absorption by the kidney; produces
vasoconstriction of blood vessels; and stimulates the
release of ACTH
