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

• Published in: Endocrine Vol. 37; no. 1; pp. 106 - 114
• Main Authors: Campino, Carmen, Carvajal, Cristian A., Cornejo, Javiera, Martín, Betty San, Olivieri, Oliviero, Guidi, Giancesare, Faccini, Giovanni, Pasini, Francesco, Sateler, Javiera, Baudrand, Rene, Mosso, Lorena, Owen, Gareth I., Kalergis, Alexis M., Padilla, Oslando, Fardella, Carlos E.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2010
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 1 - metabolism; 11-beta-Hydroxysteroid Dehydrogenase Type 2 - metabolism; 17-Hydroxycorticosteroids - chemistry; 17-Hydroxycorticosteroids - urine; 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) - metabolism; Adult; Algorithms; Chile; Chromatography, High Pressure Liquid; Cortisone - chemistry; Cortisone - urine; Diabetes; Endocrinology; Female; Humanities and Social Sciences; Humans; Hydrocortisone - chemistry; Hydrocortisone - urine; Hypertension - classification; Hypertension - enzymology; Hypertension - urine; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Mineralocorticoid Excess Syndrome, Apparent - diagnosis; Mineralocorticoid Excess Syndrome, Apparent - enzymology; Mineralocorticoid Excess Syndrome, Apparent - urine; multidisciplinary; Original Article; Oxidoreductases - metabolism; Science; Tandem Mass Spectrometry; Tetrahydrocortisol - chemistry; Tetrahydrocortisol - urine; Tetrahydrocortisone - chemistry; Tetrahydrocortisone - urine; Chile; Essential hypertension; 5β-reductase; 11β-HSD2; 11β-HSD1
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-009-9269-9

Cortisol availability is modulated by several enzymes: 11β-HSD2, which transforms cortisol (F) to cortisone (E) and 11β-HSD1 which predominantly converts inactive E to active F. Additionally, the A-ring reductases (5α- and 5β-reductase) inactivate cortisol (together with 3α-HSD) to tetrahydrometabolites: 5αTHF, 5βTHF, and THE. The aim was to assess 11β-HSD2, 11β-HSD1, and 5β-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. 11β-HSD2 enzyme activity was estimated by the F/E ratio, the activity of 11β-HSD1 in compare to 11β-HSD2 was inferred by the (5αTHF + 5βTHF)/THE ratio and 5β-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 11β-HSD2 activity. Of the remaining 86 hypertensive patients, two possessed high (5αTHF + 5βTHF)/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. 11β-HSD2 and 5β-reductase decreased activity and imbalance of 11β-HSDs should be considered in the future management of hypertensive patients.