The Adrenals and their hormones Flashcards
Where does the left adrenal vein drain into?
Renal vein
Where does the right adrenal vein drain into?
Inferior vena cava
Blood supply to adrenals
Both have many arteries
Both have only 1 vein
What is the structure of the adrenal gland from the outside to the inside?
Zona Glomerulosa (aldosterone) Zona Fasciculata (cortisol and sex steroids) Zona Reticularis (cortisol and sex steroids) Adrenal Medulla (catecholamines)
What catecholamines are produced by the adrenal medulla? What are the cells involved called?
Chromaffin cells
Adrenaline (80%)
Noradrenaline (20%)
+ Dopamine
What is the adrenal cortex comprised of?
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
What is produced in the adrenal cortex? State the 4 hormones produced.
Corticosteroids:
Mineralocorticoids: aldosterone
Glucocorticoids: cortisol
Sex Steroids: androgens and oestrogens
What are steroid hormones synthesised from? What is the consequence of this?
Cholesterol
Lipid soluble, highly influence gene transcription and translation
How many carbons in mineralcoricoids, glucocorticoids and androgens?
Mineralocorticoids: C21
Glucocorticoids: C21
Androgens: C19
Describe the production of steroid hormones
Lipoproteins deliver cholesterol to cell
Cholesterol stored in cell in fat droplets
Signal causes liberation of cholesterol by Esterase
Cholesterol driven into mitochondria by StAR protein
Cholesterol processed in mitochondria to produce steroid hormone
Different hormones are produced in different areas of the cortex due to presence of different enzymes
Whys are only low levels of sex hormones produced in the adrenal cortex?
Low presence of enzymes required to produce them
How are corticosteroids transported in the blood?
Bind to plasma proteins.
There is so much albumin that some corticosteroids will non-specifically bind to albumin.
Also more specific plasma proteins: corticosteroid binding globulin (CBG)
% of free cortisol and aldosterone in blood?
Cortisol: 10% free
Aldosterone: 40% free
What do cortisol and aldosterone bind to?
Cortisol binds to glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)
Aldosterone only binds to mineralocorticoid receptor (MR)
What type of hormone can access tissues and bind to relevant receptors?
Free unbound hormone
Describe the difference in the blood concentrations of cortisol and aldosterone
Concentration of cortisol is 1000 fold greater than the concentration of aldosterone.
How does cortisol concentration vary?
Cortisol concentration changes with the circadian rhythm. Stress hormone, so released more at times of stress.
Why do we need aldosterone if cortisol can bind to MR receptors?
Certain tissues (kidney, placenta) have a lot of 11b-hydroxysteroid dehydrogenase 2 enzyme This breaks down cortisol, so it can't act on that tissue Necessitates aldosterone
Where is renin produced?
Granular cells in kidney
What 3 stimuli increase renin production?
Renal Perfusion Pressure (RPP): If BP coming into afferent arteriole drops, sensed by granular cells, causes increased renin production
Renal sympathetic activity: If SNS is activated, renin production increases
Macular densa cells (Na+ sensors) in distal convoluted tubule: low concentration Na+ in filtered fluid, increases renin production
What does renin do?
Causes secretion of aldosterone
Increases Na+ reabsorption and water reabsorption Therefore increases BP
Mechanism of renin-angiotensin-aldosterone system
Renin acts on Angiotensinogen (from liver)
Produces Angiotensin I
Angiotensin converting enzyme (ACE) (e.g. in lungs) converts AI to AII
AII enters adrenal gland and activates aldosterone producing cells
What else can stimulate aldosterone production?
Low blood Na+
High blood K+
Describe secretion of cortisol
Corticotrophin releasing hormone (CRH) in hypothalamus is released into bloodstream
CRH delivered to anterior pituitary
Corticotrophs produce adrenocorticotrophic hormone (ACTH)
ACTH passes down to adrenal cortex to stimulate cortisol production
Negative feedback: Cortisol regulates its own production
Describe the mechanism of action of aldosterone.
Aldosterone binds to intracellular receptors and translocates to the nucleus and causes changes in transcription
Leads to increased number of Na+ channels and Na+/K+ ATPase pumps
Upregulates ability to reabsorb Na+ and indirectly increase H2O reabsorption
Where does aldosterone effect?
Late distal tubule collecting duct in kidney
Drives Na+ out of the collecting duct and back into blood
Cortisol mechanism of action
Cortisol binds to GR receptor in cell
Complex translocates to nucleus
Change in protein transcription and translation
What complexities lie in the mechanism of action of cortisol?
Can bind to 2 receptors (Glucocorticoid and Aldosterone) in most tissues
Optimum level of activation =
Full MR activation, Partial GR activation
Physiological actions of cortisol: Metabolism
Increases hepatic gluconeogenesis
Increase glycogenolysis
Increases livers capacity to make and store glucose
Stops glucose being stored peripherally
Reduces blood flow to skeletal muscle and adipose tissue
Physiological actions of cortisol: Memory
At physiological levels is pro-memory
Stress (and cortisol) wants to imprint memory as a survival technique
Cortisol increases capacity of dantate gyrus in hippocampus to respond to serotonin (adds more receptors)
Supra-physiological actions of cortisol:
Anti-inflammatory/ Immunosuppressive effects
Cortisol released to control inflammatory response at physiological level
As Cortisol levels increase becomes very anti-inflammatory and immunosuppressive (Often become ill when stressed due to high levels of cortisol)
Pathological actions of cortisol: memory
Predominantly GR activation long term
Chronically high levels of cortisol, negative effect on serotonin (anti-memory effect)
Hippocampus gets smaller
Cortisol starts destroying hippocampus and impacts ability for long term memory formation
Adrenal androgens
Synthesised in zona reticularis
= Dehydroepiandrostenedione (DHEA), DHEAS, androstenedione
Dehydroepiandrostenedione biological activity
Weak biological activity
But converted to more active androgens e.g. testosterone by enzymes in peripheral tissues
How does DHEA contribute to androgen production in men and women?
Women: substantially contributes to overall androgen production and effects
Men: very small contribution to androgen production
