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

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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.

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Acknowledgments

The authors thank Mr. Yester Nuñez of the Laboratory of Pharmacology, Faculty of Veterinary Medicine, Universidad de Chile for his valuable assistance in the determination of cortisol and its metabolites by HPLC–MS/MS. This work was supported by Fondo Nacional de Investigación Científica y Tecnológica (Fondecyt) n° 1070876 and Millennium Nucleus on Immunology and Immunotherapy Grant P04/030-F.

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Authors and Affiliations

  1. Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Lira 85, 5° Piso, Santiago, Chile

    Carmen Campino, Cristian A. Carvajal, Rene Baudrand, Lorena Mosso & Carlos E. Fardella

  2. Laboratorio de Farmacología, Universidad de Chile, Santiago, Chile

    Javiera Cornejo & Betty San Martín

  3. Section of Internal Medicine, Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy

    Oliviero Olivieri & Francesco Pasini

  4. Section of Clinical Chemistry, Department of Morphological and Biomedical Sciences, University of Verona, Verona, Italy

    Giancesare Guidi & Giovanni Faccini

  5. Departamento Medicina Familiar, Pontificia Universidad Católica de Chile, Santiago, Chile

    Javiera Sateler

  6. Departamento Ciencias Fisiológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

    Gareth I. Owen

  7. Departamento de Genética Molecular, Pontificia Universidad Católica de Chile, Santiago, Chile

    Alexis M. Kalergis

  8. Departamento Salud Pública, Pontificia Universidad Católica de Chile, Santiago, Chile

    Oslando Padilla

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  1. Carmen Campino
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  2. Cristian A. Carvajal
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Correspondence to Carlos E. Fardella.

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Campino, C., Carvajal, C.A., Cornejo, J. et al. 11β-hydroxysteroid dehydrogenase type-2 and type-1 (11β-HSD2 and 11β-HSD1) and 5β-reductase activities in the pathogenia of essential hypertension. Endocr 37, 106–114 (2010). https://doi.org/10.1007/s12020-009-9269-9

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