210
U N I T 2
Integrative Body Functions
exist between neurons in the hypothalamus that initi-
ate release of corticotropin-releasing factor (CRF) and
neurons in the locus ceruleus associated with release of
norepinephrine. Thus, norepinephrine stimulates the
secretion of CRF, and CRF stimulates the release of
norepinephrine.
16,17
Locus Ceruleus.
Central to the neural component of the
neuroendocrine response to stress is an area of the brain
stem called the
locus ceruleus
(LC).
16,17
The LC is densely
populated with neurons that produce norepinephrine
(NE) and is thought to be the central integrating site for
the ANS response to stressful stimuli (Fig. 9-3). The
LC-NE system has afferent pathways to the hypothala-
mus, limbic system, hippocampus, and cerebral cortex.
The LC-NE system confers an adaptive advantage
during a stressful situation. The SNS manifestation of
the stress reaction has been called the
fight-or-flight
response.
2
This reaction is the most rapid of the stress
responses and represents the basic survival response of
our primitive ancestors when confronted with perils of
the wilderness and its inhabitants. The increase in SNS
activity in the brain increases attention and arousal, and
thus probably intensifies memory. Increased SNS arousal
also results in heart and respiratory rate increases, moist
hands and feet, dilated pupils, dry mouth, and reduced
activity of the gastrointestinal tract.
Corticotropin-Releasing Factor.
CRF is central to the
endocrine component of the neuroendocrine response
to stress, and it is the principal regulator of the HPA
axis (see Fig. 9-3).
3,16,17
Corticotropin-releasing factor,
also known as
corticotropin-releasing hormone
, is a
small peptide hormone found in both the hypothala-
mus and extrahypothalamic structures, such as the
limbic system and brain stem. It is both an important
endocrine regulator of pituitary and adrenal activity,
as well as a neurotransmitter involved in ANS activ-
ity, metabolism, and behavior. In response to stressors,
CRF is released into the hypophysial portal vessels that
enter the anterior pituitary gland. Receptors for CRF
are distributed throughout the brain as well as many
peripheral sites. Corticotropin-releasing factor from the
hypothalamus binds to corticotropes, inducing secretion
Vigilance, cognition, focused attention
Emotional
responses
Cortisol
Alteration in
glucose, fat, and
protein metabolism
Suppression of
inflammatory and
immune responses
Supplementation and
prolongation of fight-
or-flight response
Increased heart rate and blood pressure
Pupil dilation
Dry mouth
Increased blood coagulability
Increased alertness
and arousal
Increased muscle
tension
Cerebral cortex
Thalamus
Sensory input
Reticular activating system
Spinal cord
reflexes
Limbic system
Hypothalamus
Locus ceruleus
Anterior pituitary gland
Adrenal cortex
Autonomic nervous system
Adrenal medulla
CRF
ACTH
Epinephrine
Norepinephrine
FIGURE 9-2.
Neuroendocrine pathways and physiologic responses to stress. ACTH,
adrenocorticotropic hormone; CRF, corticotropin-releasing factor.
