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

Abstract

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.

A New Presentation of the Chimeric CYP11B1/CYP11B2 Gene With Low Prevalence of Primary Aldosteronism and Atypical Gene Segregation Pattern

“…PRA was determined as described previously. 19 In accordance with our recently reported reference values for the pediatric population, 18 we consider SA level values Ͼ17.7 ng/dL (491.7 pmol/L) to be high, PRA Ͻ0.5 ng/mL per hour to be suppressed (equal to the third percentile in Chilean normotensive healthy pediatric population), and ARR levels values Ͼ10 to be high. 18 In our Chilean hypertensive adult population, the ARR level is considered high when it exceeds 25, 9 and SA is considered high when it exceeds 16 ng/dL.…”

11β-Hydroxysteroid Dehydrogenase Type 1 and the Metabolic Syndrome

“…Cortisol and 11 -HSDs have been implicated in hypertension (Anagnostis et al, 2009;Andrews et al, 2003;Campino et al, 2010;Cicala & Mantero, 2010;Edwards et al, 1988;Ferrari, 2010;Franks et al, 2004;Funder et al, 1988;Gathercole & Stewart, 2010;Y. Liu et al, 2008;Malavasi et al, 2010;Millis, 2011;Monder et al, 1989;Morales et al, 2008;Mune et al, 1995;Palermo et al, 2004;Paterson et al, 2004;Quinkler & Stewart, 2003;Raff & Findling, 2003;Stewart et al, 1996;Walker & Andrew, 2006;Walker et al, 1993;Wallerath et al, 1999;White et al, 1997).…”

“…essential hypertension (Soro et al, 1995;Walker et al, 1993) and 'salt-sensitive' hypertension (Lovati et al, 1999)] (Bailey et al, 2008;Cooper & Stewart, 2009;Henschkowski et al, 2008). Campino et al reported a high percentage of alterations in the cortisol metabolism at the pre-receptor level in hypertensive patients, previously misclassified as having essential hypertension, where 18% of the patients present reduced 11 -HSD2 activity or imbalance of 11 -HSD1 activity in comparison to 11 -HSD2 (Campino et al, 2010). As referred above, hypertension is induced in mice genetically modified to overexpress 11 -HSD1 either in the liver or AT Paterson et al, 2004).…”

A comprehensive study for the validation of a LC–MS/MS method for the determination of free and total forms of urinary cortisol and its metabolites

“…1) play different roles in human physiology and several pathological conditions [1,2]. Cortisol deficiency has been reported in patients with Addison's syndrome leading to hypotension, while excess cortisol is observed in Cushing's syndrome and determined by the onset of hypertension [3].…”