U1vi: Physiological effects of the glucocorticoids
Definition
- Glucocorticoids are hormones with a steroid nucleus, synthesised by Adrenal Cortex which binds the glucocorticoid receptor
- NOMENCALTURE: glucose + steroid + cortex
- Role in glucose metabolism, steroidal structure, synthesis by Adrenal Cortex
Synthesis Transport, Normal Values
- Cortical & corticosterone secreted by Adrenal Cortex
- 10 x more cortisol is made → finally most important glucocorticoid
- In plasma:
- 75% → bound to cortisol-binding globulin
- 15% → bound to albumin
- 10% → free → PHYSIOLOGICALLY ACTIVE
- Plasma levels 350nmol/L (diurnal variation)
- t½ 60 mins
Regulation of Secretion
- Diurnal variation in ACTH levels → ∴ diurnal variation in plasma cortisol secretion
- Negative feedback loop by cortisol + ↓ACTH
- ↑CRH → ↑ACTH → ↑Cortisol
- Circadian rhythm; peak early morning, trough middle of night
- HPA axis stimulated by trauma, ↑temp, hypoglycaemia, exercise
Metabolism
- Liver
- Converted to cortisone & excreted by glucuronidation
Physiological Effects
- Bind to receptors on nucleus → promote gene transcription → ↑mRNA & ribosomal translation
1. Insulin Sparing → Promote Hyperglycaemia
- CHO:
- ↑enzymes required for gluconeogenesis
- ↓glucose uptake by cells
- Protein:
- ↑ α-acid release by muscles
- ↑ α-acid transport into hepatocytes for gluconeogenesis
- Fat:
- Direct lipolysis
- ↑FA oxidation
- Predisposes to ketosis
2. CVS - ↑reactivity of blood vessels to catecholamines
3. GI - ↑acid + pepsin secretion → ↑tendency for peptic ulceration (2° ↓PGI synthesis)
4. HAEM
- ↑RBCs, platelets, neutrophils
- ↓LCs, eosinophils
5. Immune
- Suppresses immune system
- ↓Inflammation → stabilises lysosomes & ↓proteolytic enzymes
→ cap permeability & leakage assoc. with inflammation
- ↓BK & histamine release
6. Bone
- Osteoporosis → ↓blast collagen synthesis & ↑collagen breakdown