W2 L5: The Adrenal Gland

  • Located immediately above kidneys - enclosed in fibrous capsule surrounded by fat (5-10g)
  • 2 major functional regions:
    • adrenal cortex
    • adrenal medulla
    • Cortex & medulla posses diff. cell types w/ distinct morphology & endocrine function
  • Rich blood supply
    • Arterial blood enters cortex & passes through cord of cells
    • Blood exits via venules of medulla
    • Permits interaction b/w cortex & medulla
The Adrenal Cortex
  • Approx. 75% of adrenals
  • Characterised by intracellular lipid droplets → steroid hormone synthesis
  • 3 sub regions - all secrete diff. steroid hormones
    • Zona glomerulosa (10%)→ mineralocorticoids
    • Zona fasciculata (75%) → glucocorticoids
    • Zona reticularis (15%) → sex steroids
    • mineralocorticoids & glucocorticoids essential for life
General properties of steroid hormones
  • synthesised from cholesterol
  • Little storage in endocrine cells
    • 𝘥𝘦 𝘯𝘰𝘷𝘰 synthesis follows cell stimulus
    • stores of cholesterol present in cells can be rapidly metabolised
  • Mostly transported bound to plasma proteins
  • Steroids are lipophilic - diffuse across cell membrane into blood
  • Bind to intracellular receptors
  • Slow, long-term actions
    • regulation of transcription
Steroid hormone synthesis in synthesis in adrenal cortex
  • Sequential processing
  • Defects in 1 enzyme - cause accumulation of a precursor → shift in hormone synthesis
Mineralocorticoids
  • Regulate homeostatic control of minerals (Na+, K+/H+)
    • Cation exchange
  • 1º Mineralocorticoid → aldosterone
    • Diff. to ‘classical’ neuroendocrine regulation
    • Part of renin-angiotensin-aldosterone system (RAAS)
    • Stimulated by ↑ angiotensin II
    • Essential for Na+ maintenance
  • In plasma - mostly bound to albumin

 

Disorders of Aldosterone secretion
  • Overproduction may result from:
    • Zona glomerulosa cell hyperactivity (Conn’s syndrome)
    • Excessive renin secretion
  • Symptoms include
    • Na+ retention, K+/H+ loss
    • Hypertension (2º to Na+'/H2O retention)
    • Alkalosis (due to H+ loss)

     

 

Glucocorticoids
  • 1º glucocorticoid in humans → cortisol
  • Others → Corticosterone, cortisone
  • In plasma,
    • 75% bound to transcortin (liver glycoprotein)
    • 15% to albumin
    • 10% free/unbound
  • Multiple physiological roles:
    • metabolism
    • ↑ appetite
    • stress response (not just psychological, but also due to trauma, infection)
    • Immunosuppression
    • reduce inflammation & allergy response
    • weak mineralocorticoid activity (higher blood conc - has physiological importance)

 

Regulation of metabolism

  • Net effect = ↑ plasma glucose

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Disorders of Cortisol secretion

Cushing’s Syndrome

  • ↑ plasma cortisol caused by e.g. adrenal tumour
    • adrenal tumour
    • ↑ ACTH secretion (e.g. pituitary tumour, ↓ cortisol feedback sensitivity)
    • medication
  • Symptoms include
    • diabetes mellitus (↑ gluconeogenesis)
    • ↑ susceptibility to infection
    • muscle wasting, thin skin (↑ protein catabolism)
    • facial & trunk obesity (fat redistribution & ↑ appetite)
    • “mellon on toothpicks”

 

Addison’s Disease

  • ↓ function of adrenal cortex caused by e.g.
    • damage to adrenal or pituitary gland
    • autoimmune disease
  • Symptoms include
    • hypoglycaemia
    • lethargy, lassitude
    • loss of weight
Adrenocortical sex steroids
  • Stim. of Zona reticularis by ACTH
    • low levels of steroid secretion when compared to gonads
  • Primarily produces “pre-androgens” - converted to testosterone in target tissues
    • In women, source of approx. 1/2 androgens
    • negligible relevance in men
  • Functional significance poorly understood
    • female 2º sexual characteristics (especially body hair)?
    • mid-childhood growth spurt (pre-puberty)?
    • actions become more apparent in disease (esp ↑ secretion)
Disorders of adrenal androgen secretion
  • Excessive production
    • ↑ ACTH secretion
    • alternatives inc. adrenal tumour
  • Symtoms inc:
    • acne
    • baldness
    • hirsuitism
    • altered gonadal physiology
    • precocious puberty
The adrenal medulla
  • 1º primary cell type → chromaffin cells
    • considered specialised sympathetic postganglionic neurones
  • Contains sympathomimetic catecholamines
    • Adrenaline (80%), noradrenaline (20%)
    • derived from tyrosine, via dopamine
    • stored in vesicles
    • released by exocytosis
  • Catecholamine secretion mediated by splanchic nerves
    • stim. by stress, pain cold, anxiety
  • Functional importance in sympathetic “fight or flight” response due to acute stress

 

Action of Adrenal medulla catecholamines
  • Rapid, transient effect (compared to steroids)
    • short half life (t1/2) → few mins
  • Act via plasma membrane adrenoceptors
  • Multiple receptor subtypes allow tissue specificity of effect
  • Effect of adrenaline inc.
    • ↑ HR & Cardiac contractility
    • breakdown of glycogen & fat
    • ↑ O2 consumption
    • ↑ skeletal muscle blood flow
Disorders of adrenal medulla function
  • Pheochromocytoma→ tumour of chromaffin cells (→ ↑ catecholamine output)
  • severe hypertension
  • hyperglycaemia
  • ↑ metabolic rate
  • arrhythmias
  • anxiety

Under activity of adrenal medulla is not a clinical problem - not essential for life

Summary:

  • Adrenal have diff. functional regions: cortex (x3) & medulla:
    • Aldosterone → main mineralocorticoid - regulates ion absorption
    • Cortisol → main glucocorticoid - regulates stress response, metabolism, immune function, inflammation
    • Adrenal sex steroids - subtle effects compared to gonadal steroids
    • Catecholamines → Adrenaline & noradrenaline regulate sympathetic response to stress