Session 9: Adrenal Glands Flashcards
Location and structure of the adrenal glands. Give embryological origin.
Located just above the kidneys. Consists of two regions, an outer cortex derived from mesoderm. Inner medulla modified sympathetic ganglion (embryonic neural crest).
What are the three zones of the adrenal cortex?
GFR: Zona glomerulosa Zona fasciculata Zona reticularis
Each zone produces different (sometimes overlapping) hormones. Give each.
Salt, Sugar, Sex. The deeper you go the sweeter it gets. Mineralcorticoids like aldosterone from Zona glomerulosa Glucocorticoids like cortisol from Zona fasciculata Androgens (also glucocorticoids) forming testosterone and oestrogens.
What is steroid hormones made of?
Solubility of steroid hormones.
What type of receptors do they bind to and what do they act on?
Cholesterol
Lipid-soluble
Bind to nuclear receptors in order to modulate gene transcription.
Explain the mechanism of corticosteroids exerting their action.
Readily diffuse accros plasma membrane.
Bind to glucocorticoid receptors.
This binding causes dissociation of chaperone proteins.
Receptor ligand complex translocates to nucleus.
Dimerisation with other receptors can occur.
Receptors bind to glucocorticoid response elements (GREs) or other transcription factors.
Name of the most abundant mineralcorticoid.
Aldosterone.
Carrier protein of aldosterone.
Location of aldosterone receptor and biochemical mechanism of action.
Mainly serum albumin buth also transcortin to a lesser extent.
Intracellular receptor.
Regulates gene transcription.
What are the main actions of aldosterone?
Acts on the distal tubules and collecting ducts of nephrons in the kidney. This upregulates the expression of Na+/K+ ATPase which promotes the reabsorption of Na+ and excretion of K+. (3 Na+ out, 2 K+ in)
Since Na+ is osmotically active the reabsorption of Na+ will lead to water being reabsorbed as well. This increases blood volume and therefore also blood pressure.
It also upregulates the expression of epithelial sodium channels (ENaCs) in the collecting duct and also the colon promotin Na+ absorption.
Aldosterone also plays a major role in the renin-angiotensin-aldosterone system.
What is cortisol (glucocorticoid) synthesised and released by?
What is it stimulated by?
Released by the zona fasciculata and also synthesised by it.
Stimulated by ACTH from the anterior pituitary.
What inhibits the production of glucocorticoids?
Cortisol itself sends signals (negative feedback) to the anterior pituitary to stop the release of ACTH and also to the hypothalamus to stop the release of corticotropin releasing hormone (CRH).
What is cortisol transported by?
Transcortin (90%)
Serum albumin (10%)
Biochemical mechanism of action of cortisol.
Binds to cytoplasmic receptors. Hormone/receptor complex then enters the nucleus and interacts with specific regions of DNA.
Changes the rate of transcription of specific genes and may take time to occur.
What is CRF (from hypothalamus which will eventually cause increase in cortisol) secreted in response to?
Physical (temperature and pain), chemical (hypoglycaemia) and emotional stressors.
How does cortisol levels vary?
They vary throughout the day as ACTH is secreted with a circadian rhythm as a pulsatile secretion.
Blood cortisol peaks at around 7-9 am and is at its lowest in the late evening going up to midnight.
When would you measure cortisol levels if you suspect that the patient has insufficiency of cortisol?
You measure it when you expect cortisol to be at its highest.
Measure around 9am.
Actions of adrenaline.
Cardiovascular: Increase in cardiac output and blood supply to muscle (Increased heart rate and contractility (inotropy) by binding to beta-1
Lungs: Bronchodilation (beta-2)
Blood vessels: Vasoconstriction (if bound to alpha-1), vasodilation (if bound to beta-2)
CNS: Increased mental alertness
Carbohydrate metabolism: Increased glycogenolysis in liver and muscle
Lipid metabolism: Increased lypolysis in adipose tissue.
How does adrenaline increase heart rate?
(Biochemical mechanism)
Start after adenylyl cyclase is activated.
cAMP is produced.
cAMP can directly activate hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels (Responsible for funnny currents)
cAMP also activates PKA.
PKA phosphorylates HCN channels to modulate their function.
PKA also phosphorylates L-type Ca2+ channels to potentiate opening. This increases the slope of the upstroke of the action potential.
Explain in detail the renin-angiotensin-aldosterone system.
Hypotension and hypovolaemia leads to a decreased renal perfusion (flow of blood through the kidneys), this causes juxtaglomerular cells of the kidney nephrons to release the enzyme renin into the general circulation. This also happens in the case of a fall in Na+ plasma concentration, and increased sympathetic tone from baroreceptors.
Renin is an enzyme which cleaves angiontensinogen into angiotensin I. As the name angiotensinogen it’s an inactive precursor (zymogen). Angiotensinogen is produced and released by the liver constitutively.
Angiotensin I is still an inactive hormone, it can’t do anything without further cleavage. In the lungs angiotensin I is cleaved by Angiotensin converting enzyme (ACE) released by lung endothelial cells.
This forms the active hormone angiotensin II.
Angiotensin can now cause vasoconstriction of arterioles causing an increase in BP.
Angiotensin can also go to the posterior pituitary and stimulate the release of ADH in order to translocate aquaporin channels to aid reabsorption of water back into the blood to increase BP.
Angiotensin can also stimulate release of aldosterone from the adrenal cortex (Zona Glomerulosa) to increase the expression of Na+/K+-ATPase which leads to increased reabsorption of Na+ and water back into blood and further increases BP.
