oxidation of the hydroxyl group at the 11-beta position. 11-beta HSD1 uses the cofactor NADPH to convert biologically inert cortisone to biologically active cortisol 11-beta HSD2 uses the cofactor NAD+ to convert cortisol to cortisone Overall, the net effect is that 11-beta HSD1 serves to increase the local concentrations of biologically active cortisol in a given tissue; 11-beta HSD2 serves to decrease local concentrations of biologically active cortisol. If hexose-6-phosphate dehydrogenase (H6PDH) is present, the equilibrium can favor the activity of 11-beta HSD1. H6PDH regenerates NADPH, which increases the activity of 11-beta HSD1, and decreases the activity of 11-beta HSD2. An alteration in 11-beta HSD1 has been suggested to play a role in the pathogenesis of obesity, hypertension, and insulin resistance known as metabolic syndrome. An alteration in 11-beta HSD2 has been implicated in essential hypertension and is known to lead to the syndrome of apparent mineralocorticoid excess (SAME). A-ring reductases (5alpha- and 5beta-reductases) Cortisol is also metabolized irreversibly into 5-alpha tetrahydrocortisol (5-alpha THF) and 5-beta tetrahydrocortisol (5-beta THF), reactions for which 5-alpha reductase and 5-beta-reductase are the rate-limiting factors, respectively. 5-Beta reductase is also the rate-limiting factor in the conversion of cortisone to tetrahydrocortisone. Cytochrome P450, family 3, subfamily A monooxygenases Cortisol is also metabolized irreversibly into 6β-hydroxycortisol by cytochrome p450-3A monooxygenases, mainly, CYP3A4. Drugs that induce CYP3A4 may accelerate cortisol clearance. Chemistry Cortisol is a naturally occurring pregnane corticosteroid and is also known as 11β,17α,21-trihydroxypregn-4-ene-3,20-dione. Animals In animals, cortisol is often used as an indicator of stress and can be measured in blood, saliva, urine, hair, and faeces. See also Cortisone, a hormone Cortisol awakening response List of corticosteroids Membrane glucocorticoid receptor References External links Cortisol MS Spectrum Cortisol: analyte monograph – The Association for Clinical Biochemistry and Laboratory Medicine Anxiety Glucocorticoids Otologicals Pregnanes Stress (biology)