Adrenals and Adenohypophysial axis Flashcards
Where are the adrenal glands sat relative to other organs? (x3)
Above the kidney. Right adrenal gland is below the liver. Left adrenal gland is below the spleen.
What are the two parts of an adrenal gland?
Inner medulla. Outer cortex.
What veins do both adrenal glands drain into?
This is based on where they are sat. Left adrenal drains into the renal vein (and then the inferior vena cava). Right adrenal drains directly into the vena cava.
What is the nature of the number of veins and arteries that supply the adrenals?
They are supplied by MANY arteries that perfuse across the entire gland. But only ONE vein that takes everything away.
What are the different zones of the adrenal cortex? (x4 parts)
Adrenal cortex split into different zones (refer to photo).
Adrenal medulla, reticularis, fascitulata, glomerulosa
What class of hormones do the cortex and medulla secrete?
Adrenal medulla produces catecholamines (adrenaline and noradrenaline). Each part of the adrenal cortex produces different corticosteroids.
What is the gross anatomy of the adrenal glands?
Refer to photo. Main things to notice are the thick capsule that surrounds the adrenals, and the tributary (meaning branch) of the central vein. This means blood found in the cortex has to filter through the layers to get to the central vein.
What catecholamines are produced in the medulla, and in what proportions? (x3)
Adrenaline 80% (aka epinephrine) Noradrenaline 20% (aka norepinephrine) Dopamine (very small amount)
What cells in the medulla secrete the catecholamines?
Chromaffin cells.
What corticosteroids groups are produced in the cortex? (x3) List the major hormones for each. (x1, x1, x2)
Mineralocorticoids (aldosterone is the major mineralocorticoid) Glucocorticoids (cortisol is the major one) SOME sex steroids: these are androgens and oestrogens.
What zones of the cortex produce each corticosteroid hormone?
Zona glomerulosa – produces aldosterone. Zona fasciculata and zona reticularis – produce cortisol (and androgens and oestrogens).
What chemical is each adrenal hormone derived from? (x2)
Cholesterol is the precursor for sex steroids and cortisol – because the hormones are steroid hormones. Amines are the precursor for adrenaline!
What is the carbon structure of each of the four cortical hormones?
Mineralocorticoids and glucocorticoids are called C21 steroids because they have 21 carbons. Androgens and oestrogens – cleave more off the cholesterol backbone to produce the gonadal hormones – Androgens are therefore C19, and oestrogen C18 steroids.
How is cholesterol delivered to the relevant areas of adrenal cortex for synthesis of the corticosteroids?
- Lipoproteins deliver cholesterol into the adrenal cortical cell cytoplasm and stores as fatty acid esters. 2. When the right signal comes along, cholesterol is liberated by esterase and delivered into the mitochondria by StAR protein.
What causes different hormones to be synthesised in each zone on the adrenal cortex?
There are different enzyme balances present in the mitochondria of each zone of the adrenal cortex. This alters what hormone is synthesised from cholesterol (aldosterone, cortisol, or sex steroids).
What is the synthesis pathway of cortisol and aldosterone? Where is there a deviation in the pathway and why?
The differences in intermediates are highlighted!
CORTISOL: CHOLESTEROL –> Pregnenolone –> 17alpha-progesterone –> 11-deoxycortisol –> CORTISOL.
ALDOSTERONE: The enzyme that converts pregnenolone to 17alpha-progesterone is not present, and the pathway of pregnenolone is DIVERTED by another enzyme!
CHOLESTEROL –> Pregnenolone –> Progesterone –> 11-deoxycorticosterone –> Corticosterone –> ALDOSTERONE.
What enzyme converts corticosterone to aldosterone?
Aldosterone synthase.
How do the enzymes compare between the aldosterone and cortisol pathway?
The enzymes that convert Progesterone –> 11-deoxycorticosterone –> Corticosterone in the aldosterone synthesis pathway are THE SAME as the enzymes that convert 17alpha-progesterone –> 11-deoxycortisol –> CORTISOL.
You can see that the products in both pathways are somewhat similar.
The ONLY enzymes that differ are found in the steps: Pregnenolone –> Progesterone AND Corticosterone –> Aldosterone!
Why is corticosterone in the ALDOSTERONE pathway, considered inactive CORTISOL?
The enzymes that convert Progesterone –> 11-deoxycorticosterone –> Corticosterone in the aldosterone synthesis pathway are THE SAME as the enzymes that convert 17alpha-progesterone –> 11-deoxycortisol –> CORTISOL.
This is also why Corticosterone in the ALDOSTERONE pathway is described as an INACTIVE cortisol.
Why sex steroids synthesised in such low amounts in the adrenals?
The reason why you have only a few sex steroids is because the enzymes that are needed to synthesise them (shown in blue) are very low in the mitochondria.
What is the synthesis pathway of the sex steroids?
Only pay attention really to the enzymes in blue, and the substrates. I think that this was covered in the gonads lectures anyway.
Why are adrenal corticosteroids stored in the blood?
Lipid soluble – so blood is the store of the hormones produced in the adrenal cortex. Lipid soluble means they readily move out of the cell.
What three ways are corticosteroids stored in the blood?
CBG – corticosteroid binding globulin is a specific binding globulin. Stores aldosterone and cortisol. Albumin binds very weakly, but because there’s so much, an appreciable portion of each corticosteroid is still bound. Free and unbound.
What are the proportions that cortisol and aldosterone are found stored in the blood? What pharmacological application is there of this?
Don’t remember exactly, just need to UNDERSTAND it – as Dr B said. Aldosterone: 40% FREE, 15% CBG, 45% Albumin. Cortisol: 10% FREE, 80% CBG, 10% Albumin. Just understand, at least, that Cortisol is largely protein-bound; aldosterone is not.
Small changes in protein binding have a huge impact on the effect of Cortisol!
What receptors do cortisol and aldosterone interact?
Cortisol: Glucocorticoid receptor (GR) AND the Mineralocorticoid receptor (MR). Cortisol is not very selective. Aldosterone: Mineralocorticoid receptor (MR).
How do the concentrations of aldosterone and cortisol differ in the blood?
There is a 1000-fold difference in the concentration of aldosterone and cortisol in the blood. Cortisol: 140-690 nmol/l; Aldosterone: 140-560pmol/l. Cortex produces MORE cortisol than aldosterone.
What are the stages of the renin-angiotensin-aldosterone system?
- Renin is produced by the granular cells in the kidney.
- Renin circulates in the systemic circulation which interacts with angiotensinogen – also circulating in the blood (produced in the liver).
- This produces angiotensin I.
- Certain tissues (e.g. lung) contain angiotensin converting enzyme (ACE). So, when angiotensin I reaches a tissue containing this enzyme, angiotensin I is converted into angiotensin II.
- Angiotensin II carries out the effects of the renin-angiotensin-aldosterone system. In our case, it activates aldosterone production in the adrenal cortex.
What happens normally in the area of the nephron that the aldosterone interacts?
Normally, water and sodium move into the blood. Sodium diffuses down its concentration gradient into the distal tubule cell, and is pumped into the blood by sodium-potassium ATPase. ATPase actively pumps sodium into the blood (and pumps potassium into the distal tubule cell, which then diffuses into the tubule lumen). This active pumping maintains the concentration gradient of sodium in the tubule cell.
