11β-HSD1

11β-HSD1 converts inactive cortisone into active cortisol within tissues, particularly fat tissue and the liver. Inhibiting 11β-HSD1 reduces tissue-level cortisol activation without suppressing adrenal gland output, making it a safe and targeted intervention. Downregulation of 11β-HSD1 prevents the body from generating an adequate cortisol response even under genuine stress, producing an outcome functionally similar to cortisol resistance. Upregulation of 11β-HSD1 causes disproportionately large cortisol spikes in response to even minor stressors. Genetic 11β-HSD1 dysfunction compounds post-menopausal bone loss and fracture risk.