Adrenal Hormones Flashcards
Adrenal Glands
- Left and right adrenal gland each located atop the kidney
- Highly vascularized even more so than the thyroid
- Has distinctive layering
- 70-80% of total mass is the outer cortex
- inner core is medulla and houses specialized cells
Layers of the adrenal gland
- Cortex
- Zona glomerulosa → 15% mass
- Zona fasciculata → 50% mass
- Zona reticularis → <10% mass
- Medulla
What hormones are secreted in the layers of the adrenal cortex?
- Zona glomerulosa → aldosterone
- Zona fasciculata → cortisol and small amount of androgens
- Zon reticularis → Androgens and small amount of cortisol
- Medulla → epinephrine and norepinephrine (catecholamines)
Synthesis of adrenal cortex hormones
- All come from cholesterol
- StAR is the rate-limiting step in the production of steroid hormones → shuttling cholesterol within cells of the adrenal cortex
What type of hormones are the adrenal cortex hormones?
All steroid hormones therefore hydrophobic in nature
- receptors inside the cell
How are adrenal cortex hormones categorized?
By their function
- Mineralocorticoids (aldosterone)
- Glucocorticoids (cortisol)
- Sex hormones (androgens)
Mineralocorticoids (aldosterone) function
– Secreted from zona glomerulosa
– Regulates sodium and potassium levels
Glucocorticoids (cortisol) function
– Secreted from zonae fasciculata and reticularis
– Regulates body’s response to stress
– Regulates metabolism
Sex hormones (androgens) function
– Secreted from zonae fasciculata (a little) and reticularis (main)
– Regulate reproductive function (e.g. sex drive in females)
Aldosterone actions
At kidney
- Increases sodium reabsorption (water is also reabsorbed)
- Increases potassium secretion → lowers blood potassium levels
Overall effect: increases blood volume (blood pressure) and plasma osmolarity and lowers blood potassium concentration.
Aldosterone mechanism of action
Brought to site of action via blood supply and binding of aldosterone to its cytosolic receptor activates genes encoding for the following proteins:
- Sodium and potassium channels which are then inserted in the apical membrane (in contact with tubular fluid) → Na comes into principle cell and K goes into tubular fluid
- Sodium/potassium pumps which are then inserted in the basolateral membrane (in approximation to circulation) → Na pumped out of principle cell and reabsorbed into circulation, driving uptake of K into principle cell
- Proteins that enhance the opening of sodium and potassium channels on the apical membrane
What is aldosterones target site?
Acts on principal cells of distal tubules and collecting ducts
Regulation of aldosterone secretion
Aldosterone release stimulated by:
- High plasma potassium (hyperkalemia)
- dangerous to heart → fatal arrythmias
- Angiotensin II (low blood pressure = hypotension)
- directly stimulates release of aldosterone and helps to raise blood pressure
Renin-Angiotensin-Aldosterone system
Is a response to a drop in blood pressure accompanied by a drop in renal perfusion.
- The JG cells of the kidney secrete renin and help change angio → angio I → angio II via ACE enzyme. Angio II is a stimulant to secrete aldosterone from the adrenal gland. Aldosterone will lead to an increase in Na reabsorption and water reabsorption. The overall effect is to normalize blood pressure in response to low blood pressure as the initial stimulus
Hyperaldosteronemia
Excess aldosterone production → Primary aldosteronism
- e.g. Conn’s syndrome
- Hyperplasia of zona glomerulosa and produces extra aldosterone due to increased growth of cells here
- Increased aldosterone
- Results: hypertension, sodium retention, decreased potassium
How is cortisol release regulated?
stress is potent activator from higher brain areas which increases secretion of corticotropin releasing hormone (CRH) from the hypothalamus, increasing CRH in plasma (in hypothalamic-hypophyseal portal vessels) which then causes secretion of andrenocorticotropic hormone (ACTH), increasing ACTH in the plasma which acts on the adrenal cortex to increase cortisol secretion, increasing plasma cortisol which goes to its target cell to stimulate a response
negative feedback for cortisol release
increased plasma cortisol sends feedback to the anterior pituitary to stop the production of ACTH and also to the hypothalamus to stop production of CRH
Actions of cortisol (glucocorticoids)
- Promote energy mobilization
- Required for GH secretion (in synergism with thyroid hormones)
- Maintain vessel responsiveness to catecholamines
- Adaptive response to stress
- Clinical use: inhibit inflammation and allergic responses (low dose), immune suppression (high dose)
- Prevention of immune system rejection of transplanted organs
How does cortisol promote energy metabolism?
During stress cells need to produce more energy so more glucose produced by the liver and more fats released by adipose and can be used by cells to produce ATP in response to stress
Metabolic effects of cortisol
direct actions on liver, muscle, and adipose tissue
metabolic effects of cortisol on liver
gluconeogenesis → Increase production and secretion of glucose. Output of glucose can feed cells of body and produce ATP
metabolic effects of cortisol on muscle
protein catabolism → Not a normal part of stress response, don’t usually ask to break down protein. Muscle is metabolically effected by cortisol and can break down in chronic cases of high cortisol
metabolic effects of cortisol on adipose tissue
Lipolysis → Breaking down of stored fat to liberate FFA and glycerol. Increase of these in the blood stream can fuel cells and provide substrates to make ATP
Symptoms of abnormal secretion of cortisol
- Hyperglycemia
- Infections
- Protein depletionàwasting away of tissue
- Hypertension
- Weight gain
Hyperglycemia from cortisol
Cortisol acts on liver to make glucose and substrate released by fats can increase liver glucose and same with protein breakdown
Infections from too much cortisol
Suppressive action on immune system which would increase risk
Hypertension from too much cortisol
Can bind not only to their own receptors but also mineralcorticoid receptors (aldosterone) so have same effect as aldosterone
Weight gain from too much cortisol
Can act on the brain in feeding centres to stimulate a desire to eat. Can stimulate fatty tissue to store more fats. In visceral can stimulate lipogenesis in the abdomen so fat synthesis happens and can lead to insulin resistance. Especially if elevated chronically
Cushings Syndrome
Hypersecretion of cortisol
- characteristic of visceral obesity and fat accumulation at specific sites.
Visceral fat - Lipogenesis
Subcutaneous - lipolysis
Addison’s disease
primary adrenal insufficiency – loss of adrenal cortical function
adrenal insufficiency
General term for situation in which plasma levels of cortisol are chronically lower than normal
- Weakness, lethargy, and loss of appetite.
- Hypotension
- Hypoglycemia
- Poor tolerance for stress
- Cause usually affects aldosterone as well
- Leads to excess sodium loss and potassium retention, which causes heart arrhythmias
What are the catecholamine hormones?
- epinephrine → adrenaline (~80%)
- norepinephrine → noradrenaline (~20%)
- dopamine (~1%)
catecholamine synthesis?
Adrenal medulla
- tyrosine is the common precursor
- norepinephrine to epinephrine via enzyme PNMT
- only in the secreting cells
What happens with recurrent stress?
Lower expression of PNMT (enzyme) and decreased ability to secrete epinephrine in response to stressors
Epineephrine actions
-
Promotes energy mobilization
- Glycogen to glucose & Fat to fatty acids
- Released into blood → increasing fuel availability to produce ATP in times of stress
- Glycogen to glucose & Fat to fatty acids
-
Cardiovascular changes
- Increases heart rate
- Increases force of contraction of heart
- Increases cardiac output
- Shunting of blood from gut and skin to muscles
-
Causes bronchodilation
- oxygen to our lungs stimulating relaxation of smooth muscle in airways
Clinical use of epinephrine
Epi-Pen
- Severe allergic reaction – anaphylactic shock
- Includes: bronchospasm (or constriction of the airways) respiratory failure.
- Epi-Pen counter-acts the symptoms of anaphylactic shock
