32 - Glucocorticoid Receptors Flashcards
Glucocorticoid secretion
Glucocorticoid secretion also undergoes anormal diurnal rhythm and is a good example of how secretion of some hormones is time-dependent
What is the principal glucocorticoid receptor
The principal glucocorticoid in humans is cortisol
What is the main chemical role of glucocorticoid?
The main biochemical role of glucocorticoid is to stimulate gluconeogenesis
o This is achieved by rescuing carbon skeletons from surplus proteins (from muscle and cartilage)
What are the functions of glucocorticoid receptors?
o Suppress inflammatory response
o Stabilise plasma glucose
- Induce synthesis of enzymes of gluconeogenesis
- Transaminases
- Ketone body synthesis
- Urea cycle
o Reduces DNA synthesis and so inhibits wound healing and tissue regeneration
o Role in regulation of hypertension
What is the adrenal gland?
The adrenal gland is the centre of our stress control mechanisms
What does short term stress lead to?
Short term stress leads to the subconscious triggering of neurons
- Nerve impulses from the central nervous system enters the spinal column, where there is a synapse that involves acetylcholine
- then there is a neuron descending into the adrenal medulla which secretes noradrenaline and adrenaline into the bloodstream
The adrenaline/noradrenaline stimulate glycogen breakdown to glucose in the liver and muscle causing:
o increased blood glucose levels for energy to do exercise
o increased blood pressure due to increased heart rate
o increased breathing rate so low oxygenation of muscles
o increased metabolic rate to create more fuel molecules like fatty acis
o changes in blood flow patterns determined by different adrenaline receptors leading to decreased disgestive, excretory and reproductive activity
What adaptation is there in long term stress?
In long term stress there is another adaptation of the adrenal gland
o this is controlled by the hypothalamus which secretes CRH (corticotropic releasing hormone) into the anterior pituitary
- causes the secretion of ACTH, which travel through the bloodstream, and this then acts on receptors in the adrenal cortex to stimulate cortisol production
o this leads to breakdown of proteins and fats to provide fuel molecules that can be converted to glucose
o also, partial suppression of the immune system
What is cortisol synthesised from?
Cortisol is synthesised from acetate in the body, and we can also ingest it in the diet
What happens in the zone reticularis?
- in the zona reticularis, ACTH secreted from the anterior pituitary elevate cAMP
- this is the rate limiting step in the synthesis of cortisol
- this promotes the conversion of cortisol to pregnenolone and this is the gateway
- without this change the synthesis pathway would not happen
- pregnenolone is then converted in the zona reticularis into androgens, but in the zona fasciculata it is converted into progesterone, and through a number of hydroxylation it is converted into cortisol
Cortisol functions
o Suppress inflammatory response
o Stabilise plasma glucose
- Induce synthesis of enzymes of gluconeogenesis
- Transaminases
- Ketone body synthesis
- Urea cycle
o Reduces DNA synthesis and so inhibits wound healing and tissue regeneration
o Role in regulation of hypertension
Reponding to stress
o Glucose to pyruvate = glycolysis
- Regulated by insulin in the liver, stimulating key enzymes such as hexokinase, phosphofructokinase and pyruvate kinase
o Cortisol acts in the oppositve direction by inducing enzymes (pyruvate carboxylase, PEP carboxykinase, fructose-1,6-bisphosphatase, and gluvose-6-phosphatase)
- This drives the glycolysis pathay in reverse
The other carbon skeletons used for gluconeogenesis are:
- Lactates (acter transport from skeletal muscles to liver)
- Glycerol (generated by the breakdown of adipose triglyceride to 3 free fatty acids and glycerol- muscle contain no glycerol kinase)
Effects of glucocorticoids
o Suppression of inflammation and immune response
- Asthma
- Allergic reactions
- Autoimmune disease
- Inflammatory conditions
- Organ transplant
- Cancer therapy
o Anti-inflammatory and immunosuppressive activity reduce:
- Blood vessel dilation and leakage
- Production of mediators
- Inflammatory/ immune cell activity
Anti-inflammatory and immunosuppressive activity
o Decreased mediators:
- Glucocorticoids inhibit Phospholipase A2
- This blocks production of Arachidonic acid, prostaglandins, and leukotrienes from cell membrane phospholipid
