Principal human glucocorticoid. Synthesised from cholesterol in the zona fasciculata under HPA-axis control (CRH → ACTH → cortisol). Binds GR → nuclear translocation → transactivation (anti-inflammatory genes) and transrepression (NF-κB, AP-1). Diurnal peak 06:00–08:00, nadir 00:00. Negative feedback at hypothalamus + pituitary.
Half-Life (t½)
PO: 2h, IV: 2h, IM: 2h
Dosing Guidelines
PO: Typical 20 mg (Range: 15–30 mg)
IV: Typical 20 mg (Range: 15–30 mg)
IM: Typical 20 mg (Range: 15–30 mg)
TD: Typical 20 mg (Range: 15–30 mg)
Target Organ Systems
nervous
cardiovascular
endocrine
immune-hematologic
Interactions
Ashwagandha (caution): Ashwagandha modulates HPA — can lower diurnal cortisol in healthy adults. Not a reason to co-dose; adrenal-insufficient patients should avoid.
Pathways It Modulates
Circadian clock (activator) — endogenous GR ligand; CAR-rhythm peak ~30 min after waking