Cortisol

Cortisol is a C21 steroid synthesised on demand from cholesterol. About 90–95 % is bound in plasma, mainly to corticosteroid-binding globulin (CBG, transcortin) and albumin; the free fraction (≈5–10 %) is active. It diffuses into cells and binds the cytoplasmic glucocorticoid receptor (GR), which sheds heat-shock proteins, moves to the nucleus and activates genes with glucocorticoid response elements or represses pro-inflammatory transcription factors (NF-κB, AP-1).

Metabolic actions (anti-insulin, fuel-mobilising): increased hepatic gluconeogenesis (induction of PEPCK, glucose-6-phosphatase) and glycogen storage; muscle protein breakdown supplying amino acids; lipolysis with redistribution of fat to the trunk and face; reduced peripheral glucose uptake. Cardiovascular: permissive for catecholamine vasoconstriction (α1-receptor expression) — essential to maintain blood pressure. Anti-inflammatory and immunosuppressive: induces annexin-1 (inhibiting phospholipase A₂), suppresses COX-2, cytokines (IL-1, IL-2, TNF-α) and histamine release; causes lymphopenia and eosinopenia but neutrophilia (demargination). Other: bone loss (inhibits osteoblasts and intestinal Ca²⁺ absorption), impaired wound healing and collagen synthesis (thin skin, striae), mood and memory effects, increased free-water clearance, surfactant production and maturation of the fetal lung.

In the kidney, the enzyme 11β-hydroxysteroid dehydrogenase type 2 converts cortisol to inactive cortisone, protecting the mineralocorticoid receptor (which binds cortisol as avidly as aldosterone) from the 100–1000-fold higher cortisol concentration.