Effects of Adrenal Hormones

Function of the Adrenal Glands within the Endocrine System

Each adrenal gland contains two endocrine organs that secrete different hormone categories,
cortex (80%) and medulla (20%), in order to maintain extracellular homeostasis. The cortex has 3
layers that produce adrenocortical hormones:
• Zona glomerulosa – mineralocorticoids (aldosterone)
• Zona fasciculata – glucocorticoids (cortisol) – largest layer
• Zona reticularis – sex hormones (androgens)
However, fasciculata and reticularis can produce both sex hormones and glucocorticoids.
Adrenal glands produce and secrete rather than store therefore only small amounts of hormones
present in adrenocortical cells at one time.
Medulla contains of modified postganglionic sympathetic neurons (chromaffin cells) that do
not have axonal fibres that terminate on effector organs. They release adrenaline (80%) and
noradrenaline (20%) directly into circulation upon stimulation by the preganglionic fibre.

Roles and Regulation of Adrenocortical Hormones

1) Aldosterone
Functions:
• Increases synthesis and expression of Na+/K+ pumps in basolateral membranes of
the distal convoluted tubule and collecting duct to promote Na+ absorption into the
blood and K+ elimination via urine.
• Na+ uptake drives osmotic retention of water and increases ECF volume.
• In its absence, circulatory shock & death result due to excessive water and Na+ loss.
Regulation:
• Activated by Renin-Angiotensin-Aldosterone Pathway (RAAS)
• Rise in plasma K+ directly stimulates adrenal cortex

2) Cortisol
Functions:
• Increases blood glucose concentration via lipolysis, proteolysis, gluconeogenesis.
• Inhibits glucose uptake by many tissues, sparing it for brain.
• Enhances action of glucagon and catecholamines (permissive effects)
• Stress adaptation.
• Anti-inflammatory and immunosuppressive action.
• Glucocorticoid therapy: rheumatoid arthritis and preventing graft rejection 
Irreversible atrophy of cortisol-secreting cells
Regulation:
• Diurnal rhythm (plasma cortisol high in morning, low at night) and stress stimulate
hypothalamus to secrete CRF (corticotropic releasing factor). CRF stimulates anterior
pituitary to secrete ACTH (adrenocorticotropic hormone) that stimulates growth of
and secretion from the two inner adrenocortical layers. Cortisol is secreted and
displays negative feedback on hypothalamus.
• mostly bound to corticosteroid-binding globulin (CBG)
• proteins synthesized due to RNA transcribed by glucocorticoid target genes

• ? paracrine effects of hormone-regulated cytokines

3) Sex Hormones
 Hormone Amount Daily
(mg/day)
Cortisol 20
Aldosterone 0.1
Androgens 30

Roles and Regulation of Adrenomedullary Hormones

1) Adrenaline/Epinephrine
Functions: (Flight or Fight Responses)
• Stress Hormone (thus inhibits insulin and stimulates glucagon)
- Hepatic gluconeogenesis
- Hepatic and Muscular glycogenolysis
- Lipolysis
• Reduces digestive activity and inhibits bladder emptying (+ noradrenaline)
• Provides additional fuel to power muscular movement and nourishment for brain.
• Bronchodilation (reduces airway resistance).
• Diverts blood to and vasodilates heart and skeletal muscle vessels.
• Increases heart rate and contraction strength, increasing cardiac output and arterial
blood pressure.
• Promotes a state of arousal & increased alertness.
• Cause sweating to eliminate extra heat (+ noradrenaline)
• Flattens the lens of eye & dilates pupil.
Regulation:
• Sympathetic Control: injury, anger, anxiety, pain, cold, strenuous exercise &
hypoglycaemia generate impulses in the preganglionic fibres.
• Chromaffin cells secrete hormones into bloodstream.
• Adrenaline secreted exclusively by adrenal medulla; noradrenaline secreted by
sympathetic postganglionic fibres

Adrenocortical Hormones Levels and Disease

1) Aldosterone Hypersecretion
Causes:
• 17 α-hydroxylase deficiency
• Adrenal tumour (Primary Hyperaldosteronism/Conn’s Syndrome)
• High RAAS activity (Secondary Hyperaldosteronism)
Effects:
• Water and Na+ Retention  Increased blood volume  Hypertension
• Excessive K+ depletion  Hypokalaemia  Weakness and Fatigue

2) Cushing’s Syndrome (Cortisol Hypersecretion)

Causes:
• Adrenal Adenoma: secretes cortisol
• Anterior Pituitary Adenoma: secretes ACTH (most common)
• Ectopic Tumour: secretes ACTH (ex: abdominal carcinoma)
• Hypothalamus Malfunction: high CRF  high ACTH
Effects:
• Cortisol stimulates anti-insulin effects  proteolysis
- muscle degradation, fatigue and weakness  thin limbs
- collagen degradation  bone weakness  easily fractured
- collagen degradation  poor wound healing
- structural proteins in blood vessel walls degraded  easily bruised
• Anti-insulin effects  excessive gluconeogenesis
- Hyperglycaemia
- Glucosuria
 - Excess glucose stored as fat in face, abdomen shoulder blades  fatty
deposits stretch and weaken already protein poor abdominal skin  reddish
purple linear streaks.
• Increased adrenal androgens (by way of tumour secretion)
- In women resulting in acne, mild hirsutism & amenorrhea
- In men resulting in decreased libido and impotence

3) Adrenogenital Syndrome (Oestrogen/Androgen Hypersecretion)

Causes:
• Inherited defect in cortisol pathway  21 α or 11 β-hydroxylase deficiencies 
ACTH stimulates only androgen release  androgens inhibit hypothalamus from
stimulating gonads. Therefore, only adrenal androgens produced.
Effects:
• Newborn Females
- Male type external genitalia (enlarged clitoris)
- Female Pseudohermaphroditism
• Adult Females
- Hirsutism
- Male secondary characteristics
• Prepubertal Males
- Precocious Pseudopuberty
• Adult Males
- Overpowered by testosterone

4) Addison’s Disease (Primary Adrenocortical Insufficiency)

Causes:
• Impairment of both adrenal glands (unilateral impairment allows remaining gland
to compensate via hypertrophy and hyperplasia)
• Autoimmune destruction of adrenal cortex  undersecretion of all cortical layers
 low aldosterone and cortisol
• Pituitary/Hypothalamus Abnormality  only cortisol deficient
Effects:
• Low Aldosterone  Hyponatraemia, Hyperkalaemia, Hypotension & Low BP
• Low Cortisol  Hypoglycaemia, poor response to stress,
• Low cortisol  uninhibited ACTH  ACTH binds to MSH (melanocyte stimulating
hormone) receptors in skin and causes darkening/bronzing.
• Combined lack of glucocorticoid & mineralocorticoid can lead to vascular collapse,
shock & death.
Treatment:
• Reversal of hypotension & electrolyte abnormalities: large volumes of 0.9% saline or
5% dextrose in saline.
• Daily glucocorticoid & mineralocorticoid replacement – hydrocortisone (first line
therapy) then fludrocortisone (more potent second line therapy).

Add this to lipophilic hormone lecture

Extensively bound to plasma proteins• CBG, albumin
Binding prevents hormone entering a cell/being excreted
Unbound hormones free to interact with cell receptors & are cleared from
blood