Adrenal Hormones

Describe the control, secretions and functions of renal and adrenal hormones

This covers the production of adrenal hormones. Information specific to catecholamines receptor function can be found under adrenoreceptors, whilst detailed information on specific agents, including structure-activity relationships, is in the pharmacopeia.

The adrenal glands are paired triangular glands at the superior pole of the kidney. The gland can be divided into:

• Adrenal cortex
  Consists of three layers which produce steroid hormones (A good mnemonic is GFR for the layers, and ACT(H) for hormones)
  • Zona Glomerulosa
    Predominantly produces mineralocorticoids (aldosterone).
  • Zona Fasciculata
    Predominantly produces glucocorticoids (cortisol).
  • Zona Reticularis
    Predominantly produces sex steroids (testosterone).
• Adrenal medulla
  Produces catecholamines.

Steroid Hormones

Mineralocorticoids

Aldosterone is the key mineralocorticoid hormone, accounting for 95% of mineralocorticoid activity:

• Release is stimulated by:
  • Increased serum K⁺
  • Increased Angiotensin II
    • Hypovolaemia
    • Decreased osmolarity
  • Increased ACTH
  • Decreased serum pH
• Acts to increase sodium and water retention (and removal of potassium), via:
  • Increased expression and activation of Na⁺/K⁺ pumps on the basolateral membrane of DCT and CT cells, causing increased Na⁺ (and water) reabsorption and K⁺ elimination
  • Stimulation of the Na⁺/H⁺ pump in intercalated cells on the DCT

Glucocorticoids

Cortisol (hydrocortisone) is the primary glucocorticoid in the body, accounting for 95% of endogenous glucocorticoid effect. Cortisol is:

• Produced at ~15-30mg.day^-1
• Released in response to ACTH
  ACTH is released in response to CRH, which is:
  • Released in response to stress
  • Modulated by circadian rhythms, and demonstrates diurnal variation:
    • CRH peaks just before waking
    • CRH troughs during sleep

Cortisol has effects on many organ systems, and in physiological amounts cause:

• CVS
  • Increased sensitivity to catecholamines
  • Increases fluid retention
• Metabolic
  (Essentially anti-insulin effects):
  • Gluconeogenesis
    To provide substrates, it also stimulates:
    • Proteolysis
    • Lipolysis
  • Decreased glucose uptake

Catecholamines

Naturally occurring catecholamines include:

• Adrenaline
• Noradrenaline
• Dopamine

Synthesis of catecholamines occurs in the adrenal medulla, which is a modified sympathetic ganglion composed of chromaffin cells.

• Synthesis and release is dependent on ACh release by the presynaptic neuron
  Unlike many other hormones, catecholamine secretion is not a negative-feedback loop.

Process of catecholamine synthesis:

• Tyrosine is concentrated in the adrenal medulla
• Tyrosine is hydroxylated to DOPA by tyrosine hydroxylase
  This is the rate-limiting step, and is probably the best enzyme to remember.
• DOPA is decarboxylated to dopamine
• Dopamine is converted to noradrenaline
• Noradrenaline is converted to adrenaline by PNMT (Phenylethanolamine N-methyltransferase)
  This may only occur in the adrenal medulla.

Plasma half-lives of noradrenaline and adrenaline are small as a consequence of their metabolism and elimination.

• Extraneuronal uptake in the lungs, liver, kidney, and GIT
• Neuronal uptakeby sympathetic nerve endings
• Inactivation by MAO in nerve cytoplasm
• Inactivation by COMT in the liver and kidney

References

1. Brandis K. The Physiology Viva: Questions & Answers. 2003.
2. Chambers D, Huang C, Matthews G. Basic Physiology for Anaesthetists. Cambridge University Press. 2015.