11β-Hydroxysteroid dehydrogenase type-2 and type-1 (11β-HSD2 and 11β-HSD1) and 5β-reductase activities in the pathogenia of essential hypertension.
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.
Campino
Carmen
C
Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Lira 85, 5° Piso, Santiago, Chile.
Carvajal
Cristian A
CA
Cornejo
Javiera
J
San Martín
Betty
B
Olivieri
Oliviero
O
Guidi
Giancesare
G
Faccini
Giovanni
G
Pasini
Francesco
F
Sateler
Javiera
J
Baudrand
Rene
R
Mosso
Lorena
L
Owen
Gareth I
GI
Kalergis
Alexis M
AM
Padilla
Oslando
O
Fardella
Carlos E
CE
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D015065:17-Hydroxycorticosteroids / Q000737:chemistry / Q000652:urine*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) / Q000378:metabolism; D000328:Adult; D000465:Algorithms; D002677:Chile; D002851:Chromatography, High Pressure Liquid; D003348:Cortisone / Q000737:chemistry / Q000652:urine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000737:chemistry / Q000652:urine; D006973:Hypertension / Q000145:classification / Q000201:enzymology* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D043204:Mineralocorticoid Excess Syndrome, Apparent / Q000175:diagnosis / Q000201:enzymology / Q000652:urine; D010088:Oxidoreductases / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013760:Tetrahydrocortisol / Q000737:chemistry / Q000652:urine; D013761:Tetrahydrocortisone / Q000737:chemistry / Q000652:urine
D015065:17-Hydroxycorticosteroids; D013761:Tetrahydrocortisone; D013760:Tetrahydrocortisol; D010088:Oxidoreductases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468386:HSD11B1 protein, human; C468387:HSD11B2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C051860:cholestenone 5 beta-reductase; D003348:Cortisone; D006854:Hydrocortisone