11beta-hydroxysteroid dehydrogenase type-2 and type-1 (11beta-HSD2 and 11beta-HSD1) and 5beta-reductase activities in the pathogenia of essential hypertension

Cortisol availability is modulated by several enzymes: 11beta-HSD2, which transforms cortisol (F) to cortisone (E) and 11beta-HSD1 which predominantly converts inactive E to active F. Additionally, the A-ring reductases (5alpha- and 5beta-reductase) inactivate cortisol (together with 3alpha-HSD) to tetrahydrometabolites: 5alphaTHF, 5betaTHF, and THE. The aim was to assess 11beta-HSD2, 11beta-HSD1, and 5beta-reductase activity in hypertensive patients. Free urinary F, E, THF, and THE were measured by HPLC-MS/MS in 102 essential hypertensive patients and 18 normotensive controls. 11beta-HSD2 enzyme activity was estimated by the F/E ratio, the activity of 11beta-HSD1 in compare to 11beta-HSD2 was inferred by the (5alphaTHF + 5betaTHF)/THE ratio and 5beta-reductase activity assessed using the E/THE ratio. Activity was considered altered when respective ratios exceeded the maximum value observed in the normotensive controls. A 15.7% of patients presented high F/E ratio suggesting a deficit of 11beta-HSD2 activity. Of the remaining 86 hypertensive patients, two possessed high (5alphaTHF + 5betaTHF)/THE ratios and 12.8% had high E/THE ratios. We observed a high percentage of alterations in cortisol metabolism at pre-receptor level in hypertensive patients, previously misclassified as essential. 11beta-HSD2 and 5beta-reductase decreased activity and imbalance of 11beta-HSDs should be considered in the future management of hypertensive patients.