Neuroendocrinology of the Stress Response

What is Stress?

illness injury lack of water swarms of locust malnourishment physical exhaustion predation lack of control loss of loved one mid-term exams

These are all things that are STRESSORS in other words, they can cause a STRESS RESPONSE

STRESSOR: anything that disrupts the body'd physiological balance

STRESS-RESPONSE: body's adaptations to stressors

The stress-response includes two endocrine responses (from the same endocrine gland - the adrenal). The adrenal cortex releases glucocorticoids (about 50 diffent related hormones); the adrenal merdulla releases epinephrine.

These two endocrine responses comprise the two primary components of the stress response.

Hans Seyle characterized the response of the adrenal cortex the General Adaptation Syndrome (as he assumed that the body was exhibiting an adaptive response to stress - which is only true part of the time)

Walter Cannon characterized the response of the adrenal medualla to release epinephrine (in conjunction with the sympathetic nervous system activation which triggers the activation of the adrenal medulla) as the fight or flight response.

The goal of these systems is to maintain homeostasis - to buffer the internal environment from the external environment.


1) Brain

2) Hypothalamus induced to release CRH and related secretagogs as well as activation of vasopressin/oxytocin neurons

Sympathetic Nervous System (SNS) activated

(Parasympatetic (PSNS) system inhibited)

3) CRH and related ... act on the pituitary to release ACTH and prolactin

Oxytocin and vasopressin released from posterior pituitary

Sympathetic nervous system releases norepinephrine and stimulates epinephrine r elease from adrenal medulla

4) ACTH induces the release of glucocorticoids from the adrenal cortex


1) Parasympathetic Nervous System

Hypothalamus: GnRH, GHRH, somatostatin release inhibited

2) Pituitary: release of GH, LH and FSH inhibited

3) Liver the somatomedins are inhibited

Gonads, the production of estrogen, progesterone and testosterone are inhibited.

What the effects of stress on the Peripheral Nervous System (PNS= Symp. NS + Parasymp. NS)

sympathetic NS organs parasympathetic NS

decrease secretion salivary glands salivate

speed up heart slow down

secrete adrenal gland

don't digest intestines digest

hold back bladder empty

"flight or fright" "digestive



1. There is a need for immediate energy/ energy storage is prevented

-> increase glucose in blood stream

1) glucocorticoids prevent glucose uptake by cells

2) glucagon mobilizes stored glycogen

3) insulin is inhibited (no glucose storage)

-> oxygen must be delivered to muscles and other cells

1) breathing rate increases (sympathetic NS)

2) heartrate increases (symp NS)

3) blood pressure increases (symp + vasopressin)

4) water is retained to increase blood volume (vasopressin)

2) Anabolic Processes are inhibited (why waste energy on processes important tomorrow?)

-> digestion is curtailed

-> reproductive processes are inhibited

-> immune system inhibited

-> suppression of inflammation

-> no pain perception "stress induced analgesia"

Let's look more closely at the stress response.


excess fats are stored in adipose tissue as triglycerides

amino acids are stored as proteins

glucose is stored as glycogen

-> Insulin is the key hormone for glucose storage

-> glucocorticoids, glucagon and catecholamines collectively reverse insulin's effect

-> glucose uptake is inhibited

-> protein synthesis is inhibited

-> fatty acid synthesis is halted

-> triglycerides and glycogen and proteins are degraded

Acute effect: more fuel to provide energy

Chronic effect: fatigue, diabetes, muscle atrophy


increased heart rate (adrenal medulla & SNS)

increased blood volume (vasopressin)

increased blood pressure (adrenla medulla & noreinephrine)

Acute effect: increased cardiovascular tone to speed delivery of glucose and oxygen to tissues that need it.

Chronic effect: chronic hypertension, damaged heart muscle, weakened blood vessels, etc -> heart disease & hypertension


digestion is inhibited (enzymes and hormone, perstalsis)

dry mouth

prolonged stress: gastric ulcers

stomach usually expends energy repairing stomach mucosa, this is curtailed with stress. Ulcer repair is usually facilitated by prostaglanding, which are inhibited by stress.


GnRh release inhibited in hypothalamus by beta-endorphin and CRH

prolactin release causes the pituitary response to GnRH to be inhibited (decreasing LH and FSH release)

adrenal secretion of androgens in female impairs reproduction at level of ovary

glucocorticoids inhibit gonadal response to LH and FSH

in males erection requires parasympathetic tone; ejaculation requires sympathetic tone -> either impotency or premature ejaculation results


stress inhibits growth hormone and other anabolic processes

chronic effects - in young = stress induced dwarfism

in adults = loss of bone density and muscle, skin texture poorer


beta-endorphins, enkephalins, dynorphins, endogenous opiates are released during stress (found in the brain, pituitar, and gut)

This system seems to habituate in response to chronic pain, so chronic pain occurs without continued analgesia


lymphocytes produce cells to fight off disease. In the Bone marrow the cells produced are called "B" cells - these cells make antibodies. In the thymus, these cells are called "T" cells - which do many things.

1. An invading pathogen is first detected by a macrophage cell in the blood, which release interleukin-1

2. The T-helper cell responds by releasing interleukin-2 and B-cell growth factor

3. Interleukin-2 triggers T-cell proliferation; B-cell growth factor induced proliferation of B-cells which make antibodies to the invading pathogen

4. The antibodies to the pathogen immobilize the pathogen; T-cells induce cytotoxic killer cells that destroy the invading pathogen

-> the immune system also activates immunosuppression at the same time the immune response is being induced by triggwering glucocorticoid release.

-> glucocorticoids inhibit T-cells, B-cells, and cytotoxic killer cells.

The immune system activates immunosuppression at the same time the immune response is being induced. Thus, with chronic stress there is a depression of the immune systems and increased disease. In animals like rats -> stressors aid in the establishment and growth of tumors and there is imparied disease resistance. In humans data to support increased cancer risk with chronic stress is minimal.

Chronic stress can also lead to brain damage.

There are glucocorticoid receptors throughout the brain, but the hippocampus has a particularly high number of them. This is because normally the hippocampus serves as a "brake" on the stress response, dampening the system at the level of the hypothalamus so that less of a response is induced. Unfortunately chronic stress with elevated glucocorticoid secretion leads to hippocampal damage. This is because glucocorticoids reduce glucose uptake and neurons require glucose for energy. Since hippocampal neurons re very active, the lack of glucose can lead to neuronal death.

So, the stress response is good response to acute stress, but an unhealthy response to chronic stress.



Initially physiologists dominated the study of the stress response. They studies the effects of large amounts of stress on animals and recorded robust responses, in terms of hormonal and PNS responses. Then, psychologists began getting involved in the story, and (according to the physiologists) made the story a bit more complicated - but also more interesting.

The person who had the biggest impact on the field of stress, from the psychological perspective, was John Mason. He conducted experiments that demonstrated that the response to stressors is modulated by psychological factors.

The factors that affect the stress response are: 1) lack of control; 2) lack of predictability; and 3) lack of outlets for frustration.


Mason conducted an experiment with 2 rats. One rat was in an operant conditioning unit in which a light came on to predict that foot shock was about to be delivered