Adrenal glands

Where are the adrenal glands located?

above the upper poles of the kidneys (suprarenal glands) - lie against the diaphragm in the retroperitoneal space

Where does the adrenal gland receive blood from?

receive blood supply also directly from the aorta - blood drains through the suprarenal vein to the left renal vein or directly to the inferior vena cava on the right

Name the layers of the adrenal gland starting from the top

Zona glomerulosa

Zona fasiculata

Zona reticularis

Chromaffin cells (medulla)

What does the adrenal medulla secrete and what cells is it made up of?

Chromaffin cells

Hormones: adrenaline + noradrenaline

What does the adrenal cortex secrete and what are the layers?

Zona glomerulosa: mineralocorticoids eg. Aldosterone

Zona fasiculata: glucocorticoids eg. Cortisol

Zona reticularis: glucocorticoids and androgens eg. testosterone

What does cortisol bind to in the blood?

Cortisol-binding globulin

Properties of aldosterone

lipophilic and so in blood binds mainly to serum albumin & to a lesser extent corticosteroid-binding globulin (CBG)

Where does aldosterone act and what does it do?

• component of the renin-angiotensin-aldosterone system (RAAS)

• Mainly acts in the distal tubules and collecting ducts of nephrons in the kidney where it promotes expression of Na+/K+ pump, causing reabsorption of Na+ and excretion of K+, -> influencing water retention & blood volume -> affects blood pressure

What affects secretion of Aldosterone?

• increases K+ ion conc in ECM → increases aldosterone secretion

• Imcrease ANG II in ECM → increases aldosterone secretion

• Increase Na+ in ECM → slightly decreases aldosterone secretion

• Increased atrial natriuretic peptide (ANP) → decreases aldosterone secretion

• ACTH is needed for secretion but does not control it

What drugs can you give to someone with an over active RAAS ?

• ACE inhibitors) reduce the formation of angiotensin Il and are the most widely used

• Angiotensin Il receptor blockers (ARBs) can be also used to block the actions of angiotensin lI

• Inhibitors of renin (direct renin inhibitors)

What does cortisol do and when is it released?

Inhibits CRH & ACTH release via negative feedback to hypothalamus & anterior pituitary (HPA axis: hypothalamic-pituitary-adrenal axis )

Released due to stress

Cortisol effect on carb metabolism

• stimulate gluconeogenesis

• Causes mobilisation of A.A from extrahepatic tissues (muscle)

• Atangonist to insulin

Effects of cortisol on protein synthesis

Decreases protein synthesis and increases catabolism of proteins in the cells → can lead to proximal myopathy

Lower I,Munich functions of lymphoid tissues

Effects of cortiosl of fat metabolism

Promotes mobilisation of F.A from adipose tissue→ increase conc of F.A in the plasma

Enhances oxidation of FlA

Shifts metabolism to use fats nir glucose for energy

Cortisols effect on inflammation

Prevents and reduces Inflammation

• stabilise lysosomal membranes

• Decrease permeability of capillaries

• Decrease migration of Shute blood cells

• Reduces release of interlukein 1

• Suppresses the immune system

What is ACTH made from?

ACTH (39 amino acids) derived from pro-opiomelanocortin (POMC; ~250 amino acids)

Why do patients with high ACTH have hyperpigmentation?

MSH (melenain secreting hormone) and ACTH are both made from POMC and have a similar structure.

When is ACTH released?

• released in pulses that follow a circadian rhythm

• ACTH peak plasma levels occur early in the morning and lowest levels (nadir) late in the evening

Action of ACTH

** ACTH is hydrophilic and acts on high affinity GPRCs on the plasma membrane of target cells in the zona fasciculata & reticularis

GPCRs for ACTH are a MC2 which use CAMP as a second messenger

ACTH binding leads to activation of cholesterol esterase, increasing the conversion of cholesterol esters to free cholesterol

What are DHEA and androstenedione and what do they do?

Dehydroepiandrosterone (DHEA) and androstenedione are weak androgens

• Partially regulated by ACTH and CRH

• In males: DHEA is converted to testosterone in the testes

• In females: adrenal androgens promote libido and are converted to oestrogens by other tissues (after menopause this is only source of oestrogens)

• Promote axillary and pubic hair growth in both sexes

Why does the adrenal gland not have axons?

The Chromaffin cells act as postgamglionic nerve fibres

What are the different types of adrenergic receptors?

• α1 receptors facilitate an increase in intracellular Ca2+ by coupling to Gαq

• α2 receptors facilitate a decrease in the intracellular second messenger cAMP by the inhibitory G protein Gαi

•  β type has three subtypes (β1, β2 and β3): all promote increase in cAMP by coupling to the stimulatory G protein Gαs