Lecture 28 - Cortisol and stress Flashcards
Cortisol
Produced as it is required (steroid hormone made from cholesterol as it is required since it is lipid soluble)
Carried in blood bound to carrier protein
Travels to target cell and passes through the cell membrane. Binds to a specific receptor. Moves into nucleus. Activates specific genes. mRNA is formed which produces protein. This protein has an effect
The effect is slow - often hours to days
Lipid soluble hormone released by the middle layer of the adrenal cortex
Stress and non-stress neural inputs - such as day-night rhythm and low blood glucose concentration
Sequence of events that lead to cortisol secretion and the response from target cells
Stimulus input can be stress e.g. infection, cold temperature or non stress e.g. day-night rhythm, low blood glucose concentration neural inputs
In response to the stimulus the hypothalamus releases corticotropin-releasing hormone (CRH)
CRH travels to the anterior pituitary stimulating it and causing release of adrenocorticotropic hormone (ACTH)
ACTH travels in the bloodstream to the adrenal glands (cortex) where it binds to cells within the middle layer of the adrenal cortex because these cells have the correct receptors causing cortisol synthesis and release (produced as required)
Cortisol travels to the muscle, fat and liver and has metabolic effects as well as other effects
Cortisol secretion is controlled mainly by negative feedback EXCEPT during the stress response (the stressful stimulus overrides the negative feed back system)
Cortisol inhibits the secretion of CRH and ACTH through negative feedback
Effects on the target cells with the release of cortisol
Muscle - increased protein breakdown and decreased glucose uptake
Fat - increased fat breakdown and decreased glucose uptake
Liver - increase in glucose synthesis (gluconeogenesis)
Other effects
Helps one to cope with stress
Long-term - suppresses the immune system
Essential for maintain normal blood pressure
Note that at the target cells cortisol binds to receptors in the cytoplasm and activates gene transcription to produce the above responses
Cortisol secretion - daily pattern
Cortisol daily pattern…
Pulses during day
Highest peak upon waking and often drops to its lowest point in the early part of sleep
Can change when sleep pattern is disturbed e.g. jet lag (cortisol will be higher at these times)
Cortisol functions
Increasing blood glucose levels
Increasing fat, protein and carbohydrate metabolism to maintain blood glucose
Promoting anti-inflammatory actions
Increasing blood pressure
Increasing heart and blood vessel tone and contraction
Activation of the CNS
Hyposecretion
The hormone levels are too little (or none)
Hypersecretion
The hormone levels are too high
Hyposensitive
The hormone receptors have little (or no) response
Hypersensitive
The hormone receptors respond to much to the hormone
What are problems in hormonal signalling caused by?
Autoimmunity - destruction of receptors (or artificial stimulation of receptors)
Genetic mutation - Mutations can cause gain or loss of function
Tumours - excess tissue usually leads to excess hormone release, but can sometimes prevent release
Other - many other factors can disrupt hormonal signalling
Low cortisol secretion could be described as
hyposecretion, caused by autoimmunity or other factors e.g. Addisons disease
Addison’s disease
Lowered secretion of both cortisol and aldosterone
Low cortisol concentration leads to increased ACTH
Excess ACTH stimulates melanin synthesis therefore there is a change in skin pigmentation (before treatment have darkening of the skin)
Other symptoms include low blood pressure, weakness (lack of fuel), Unexplained weight loss, fatigue, low blood sodium etc etc
All due to the lack of adrenal cortex hormones
Increased cortisol levels could be described as
Hyper secretion, caused by tumours or other factors e.g. cushings syndrome
Cushing’s syndrome
Too much cortisol
High blood pressure, weakness (muscle wasting caused by the muscle being metabolised), buffalo hump (deposition of fat on the upper back), moon face (very rounded face - although there is fat metabolism in usual adipose tissue, you get fat deposition in unusual places (face and back) due to redistribution of body fat)
Treat with medications or removal of tumourous adrenal gland
Can happen in many ways:
Hyper secretion of ACTH due to pituitary tumour
Hyper secretion of cortisol due to adrenal tumour
High use of steroidal medication
What is stress?
condition such as a threat, challenge or physical and psychological barrier
Stress response
Stress stimulus activated the hypothalamus. The hypothalamus organises a response and activates the adrenal glands, sympathetic nervous system and the (posterior lobe of the) pituitary gland. This causes the body to respond as a result of the hypothalamus initially responding.
Integrated stress response
Stress activated the hypothalamus which causes the release of 3 hormones
Cortisol (adrenal cortex) - increase blood glucose and blood pressure
Process is that hypothalamus secretes CRH which stimulates the anterior pituitary to secrete ACTH which stimulates the adrenal cortex to synthesise and secrete cortisol which stimulates increase in blood glucose (gluconeogenisis in the liver) and increase in blood pressure.
Adrenaline (adrenal medulla) - increases blood glucose, blood pressure and heart rate
Process it that the hypothalamus sends action potentials down sympathetic preganglionic fibres and synapse in the adrenal medulla. The adrenal medulla is now stimulated and secretes adrenaline. The release of adrenaline stimulated the increase of blood glucose (glycogenolysis in liver and skeletal muscle), increases the heart rate (effects the pace maker cells and muscle) and increases blood pressure.
ADH (posterior pituitary) - decrease water excretion (increase in blood volume and blood pressure)
Process - the hypothalamus sends action potentials down the neuronal connections and cause hormone release. These action potential stimulate the posterior pituitary which secrets ADH (antidiuretic hormone). This hormone stimulates decrease in water excretion (in kidneys), increase in blood volume and an increase in blood pressure
This causes an overall body response to hopefully get rid of the stressor (flight or fight)
Alarm phase of the stress response
The stressor upsets homeostasis or cellular balance
Increase in heart rate and force of contraction, changes in diameter of peripheral vessels and changes in pupil diameter
Increased mental alertness
Increased energy used by all cells
Mobilisation of glycogen and lipid reserves
Changes in circulation
Reduction in digestive activity and urine production (as they are not essential)
Increased sweat gland secretion
Increased heart rate and respiratory rate
Resistance phase of the stress response
Body fights back by adjusting to the stress. The body tries to become balanced (a process called homeostasis).
More serious effects with prolonged periods of heightened cortisol
Increase in blood pressure for example - prolonged hypertension can lead to negative effects on the cardiovascular tissue
Exhaustion phase of the stress response
There is a break down of homeostatic regulation
Can end in death unless the stress is removed
Run out of stores of energy, the heart has been worked way too hard for way too long therefore there may be a risk of a heart attack
Usually die of heart failure
Why can some stresses be good?
Some help you response effectively to a situation
Overcoming the stress response
During the stress response there is an override of the normal negative feedback loop for cortisol release and you have prolonged release of other hormones in the body therefore to manage this you have to overcome the stress/remove the stressful stimuli so that hormone levels can be bought back to the point that they should be at
Prolonged stress can have…
negative health effects
Thyroid tumour
Excess of thyroid tissue which may also be releasing thyroid hormone but because it is tumourous tissue it may not be under the same regulatory control as the normal thyroid tissue
This can cause a problem in hormonal signalling
Acute vs prolonged stress
Acute stress has many physiological effects, both hormonal and neural. Prolonged stress can have negative health effects
