Adrenal Gland

The adrenal gland is split into the adrenal medulla and the cortex, which itself is subdivided into 3 sections.

The glands are found above the kidneys and are supplied by superior, middle and inferior adrenal arteries.

Medulla – This is at the centre of each adrenal gland.

– Made up of chromaffin cells producing noradrenaline (20%) and adrenaline (80%)

– Driven by sympathetic preganglionic fibres which synapse in medulla

– Considered a specialised sympathetic ganglion which releases secretions into the blood.

Cortex – This is the outermost layer of the adrenal gland which is split into 3 zones:


i) Zona glomerulosa

This is the outermost zone of the adrenal cortex.

– This is responsible for the production of aldosterone, a mineralocorticoid, which is made by the enzyme aldosterone synthase.

– This is part of the renin-angiotensin system and acts to increase blood pressure by increasing reabsorption of sodium from the kidneys.

ii) Zona fasciculata

This is situated between the zona glomerulosa and reticularis.

– It is the largest layer of the adrenal cortex.

– Responsible for producing glucocorticoids like cortisol through the HPA axis.

Cortisol synthesis is stimulated by the release of corticotrophin-releasing factor from the hypothalamus.

– Stimulates production of ACTH from anterior pituitary gland

– This acts on the adrenal cortex to directly stimulate cortisol synthesis and some mineralocorticoid release.


Cortisol exerts its effects by binding the glucocorticoid receptor within nuclei and causing transcription of specific genes.

Metabolic actions:

i) Counters insulin – increases gluconeogenesis and decreases uptake by fat/muscle increasing blood glucose

ii) Increases protein breakdown and reduces protein synthesis

Immune Actions:

i) Decreases T and B cell proliferation

ii) Decreases production of inflammatory cytokines IL-12 and TNFa

iii) Increases production of anti-inflammatory cytokines IL-10

iv) Switches from Th1 –> Th2 response

Other actions: Cortisol also changes one’s mood and suppresses reproductive function.

– Inhibits bone formation and collagen synthesis in the skin  and stimulates gastric acid secretion


Because the steroid has these actions, prolonged exposure to steroids has a number of side effects:


– Infection, due to immunosuppression

– Poor wound healing

– Osteoporosis, due to osteoblast inhibition

– Hyperglycaemia (steroid-induced diabetes)

– Muscle wasting due to protein catabolism

– Thinning of the skin

– Weight gain

– Cataracts and Glaucoma


Steroid use also suppresses the HPA due to its negative feedback actions, so sudden withdrawal is avoided. This is because it can lead to adrenal insufficiency, as patients cannot synthesise their own steroids.


iii) Zona reticularis

This is the innermost layer of the adrenal cortex, which produces precursor androgens including DHEA and androstenedione from cholesterol.

– These precursors can be converted in the adrenal cortex or are released into the blood stream where they are taken up by testes/ovaries and made into testosterone and estrogen.

– ACTH partially regulates adrenal androgen secretion and so is seen as a permissive factor.

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