Journal of the American Society of Hypertension
Volume 2, Issue 4 , Pages 286-293 , July 2008

Correlation of glycyrrhetinic acid–like factors (kidney 11β-HSD2-GALFs) with urinary free cortisol and plasma renin activity in essential hypertension

  • David J. Morris, DPhil

      Affiliations

    • Department of Pathology and Laboratory Medicine, The Miriam Hospital, Brown University Medical School, Providence, Rhode Island, USA
    • Corresponding Author InformationCorresponding author: David J. Morris, DPhil, Department of Pathology and Laboratory Medicine, The Miriam Hospital, Brown University Medical School, 164 Summit Avenue, Providence, Rhode Island 02906. Tel: 401-793-4231; fax: 401-274-5154.
  • ,
  • Syed A. Latif, PhD

      Affiliations

    • Department of Pathology and Laboratory Medicine, The Miriam Hospital, Brown University Medical School, Providence, Rhode Island, USA
  • ,
  • Ying H. Lo, PhD

      Affiliations

    • Department of Pathology and Laboratory Medicine, The Miriam Hospital, Brown University Medical School, Providence, Rhode Island, USA
  • ,
  • Kofi Abrampah, DPharm

      Affiliations

    • Department of Pathology and Laboratory Medicine, The Miriam Hospital, Brown University Medical School, Providence, Rhode Island, USA
  • ,
  • Andrew S. Brem, MD

      Affiliations

    • Rhode Island Hospital, Brown University Medical School, Providence, Rhode Island, USA
  • ,
  • W. Reid Lichtfield, MD

      Affiliations

    • Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  • ,
  • Gordon H. Williams, MD

      Affiliations

    • Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA

Received 22 October 2007 ,Accepted 2 January 2008.

References 

  1. Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CHL, Edwards CRW. Mineralocorticoid activity of liquorice (11β-hydroxysteroid dehydrogenase deficiency comes of age). Lancet. 1987;2:821–824
  2. Epstein MT, Espiner EA, Donald RA, Hughes H, Cowles RJ, Lun S. Licorice raises urinary cortisol in man. J Clin Endocrinol Metab. 1978;47:397–400
  3. Kornel L, Starnes WR, Holl SR, Hill A. Studies on steroid conjugates: VI. Quantitative paper chromatography of urinary corticosteroids in essential hypertension. J Clin Endocrinol Metab. 1969;29:1608–1617
  4. Walker BR, Stewart PM, Shackleton C, Padfield PL, Edwards CRW. Deficient inactivation of cortisol by 11β-hydroxysteroid dehydrogenase in essential hypertension. Clin Endocrinol. 1993;39:221–227
  5. Ulick S, Levine LS, Gunczler P, Zanconato G, Ramirez LC, Rauh W, et al. A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol. J Clin Endocrinol Metab. 1979;49:757–764
  6. Wilson RC, Harbison MD, Krozowski ZS, Funder JW, Shackleton CH, Hanauske-Abel HM, et al. Several homozygous mutations in the gene for 11β-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1995;80:3145–3150
  7. White PC, Mune T, Agarwal AK. 11β-hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocrine Rev. 1997;18:135–156
  8. Whitworth JA, Gordon D, McLachlan-Troup N, Scoggins BA, Moulds RW. Dexamethasone suppression in essential hypertension: effects on cortisol and blood pressure. Clin Exp Hypertens. 1989;11:323–335
  9. Kelly JJ, Mangos G, Williamson PM, Whitworth JA. Cortisol and hypertension. Clin Exp Pharmacol Physiol Suppl. 1998;25:S51–S56
  10. Watt GC, Harrap SB, Foy CJ, Holton DW, Edwards HV, Davidson HR, et al. Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four-comers approach to the identification of genetic determinants of blood pressure. J Hypertens. 1992;10:473–482
  11. Walker BR, Phillips DI, Noon JP, Panarelli M, Andrew R, Edwards HV, et al. Increased glucocorticoid activity in men with cardiovascular risk factors. Hypertension. 1988;31:891–895
  12. Litchfield WR, Hunt SC, Jeunemaitre X, Fisher NDL, Hopkins PL, Williams RR, et al. Increased urinary free cortisol; a potential intermediate phenotype of essential hypertension. Hypertension. 1998;31:569–574
  13. Chamarthi B, Kolatkar NS, Hunt SC, Williams JS, Seeley EW, Brown NJ, et al. Urinary free cortisol: an intermediate phenotype and a potential genetic marker for a salt-resistant subset of essential hypertension. J Clin Endocrinol Metab. 2007;92:1340–1346
  14. Lo YH, Sheff MF, Latif SA, Ribeiro C, Silver H, Morris DJ. Kidney 11β-HSD2 is inhibited by glycyrrhetinic acid-like factors (GALFs) in human urine. Hypertension. 1997;29:500–507
  15. Morris DJ, Lo YH, Lichtfield WR, Williams GW. Impact of dietary Na+ on glycyrrhetinic acid-like factors (kidney-11β-HSD2 GALFs) in human essential hypertension. Hypertension. 1998;31:469–472
  16. Soro A, Ingram MC, Tonolo G, Glorioso N, Fraser R. Evidence of coexisting changes in 11β-hydroxysteroid dehydrogenase and 5β-reductase activity in subjects with untreated essential hypertension. Hypertension. 1995;25:67–70
  17. Tuck ML, Williams GH, Cain JP, Sullivan JM, Dluhy RG. Relation of age, diastolic pressure and known duration of hypertension to presence of low renin essential hypertension. Am J Cardiol. 1973;32:637–642
  18. Emanuel RL, Cain JP, Williams GW. Double antibody radioimmuno-assay of renin activity and angiotensin II in human peripheral plasma. J Lab Clin Med. 1973;81:632–640
  19. Williams GH, Dluhy RG, Lifton RP, Moore TJ, Gleason R, Hunt SC, et al. Non-modulation as an intermediate phenotype of essential hypertension. Hypertension. 1992;20:788–796
  20. Bland JM, Altman DG. Transforming data. Br Med J. 1996;312:770–775
  21. Tomlinson JW, Walker JW, Bujalska IJ, Draper N, Lavery GG, Cooper MS, et al. 11β-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocrine Rev. 2005;25:831–866
  22. Edwards CR, Stewart PM, Burt D, Brett L, McIntyre MA, de Kloet WS, et al. Localization of 11β-hydroxysteroid dehydrogenase–tissue specific protector of the mineralocorticoid receptor. Lancet. 1998;2:986–989
  23. Funder JW, Pearce PT, Smith R, Smith AI. Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science. 1988;242:583–585
  24. Brem AS, Bina RB, King TC, Morris DJ. Localization of two 11β-OH steroid dehydrogenase isoforms in aortic endothelial cells. Hypertension. 1998;31:459–462
  25. Hatakeyama H, Inaba S, Miyamori I. 11β-hydroxysteroid dehydrogenase in cultured human vascular cells. Hypertension. 1999;33:1179–1184
  26. Tian-Quan C, Wong B, Mundt SS, Thieringer R, Wright SD, Hermanowski-Vosatka A. Induction of 11β-hydroxysteroid dehydrogenase type-1 but not type-2 in human aortic smooth muscle cells by inflammatory stimuli. J Steroid Biochem Molec Biol. 2001;77:117–122
  27. Souness GW, Brem AS, Morris DJ. 11β-hydroxysteroid dehydrogenase antisense affects vascular contractile response and glucocorticoid metabolism. Steroids. 2002;67:195–201
  28. Pirpiris M, Sudhir K, Teung S, Jennings G, Whitworth JA. Pressor responsiveness in corticosteroid-induced hypertension in humans. Hypertension. 1992;19:567–574
  29. Ullian ME, Walsh LG. Corticosterone metabolism and effects on angiotensin II receptors in vascular smooth muscle. Circ Res. 1995;77:702–709
  30. Gorsline J, Latif SA, Morris DJ. Changes in 5α- and 5β-reductase pathways of aldosterone metabolism by dietary sodium. Am J Hypertension. 1988;1:272–275
  31. Latif SA, Pardo HA, Hardy MP, Morris DJ. Endogenous selective inhibitors of 11β-hydroxysteroid dehydrogenase isoforms 1 and 2 of adrenal origin. Mol Cell Endocrinol. 2005;243:43–50
  32. Morris DJ, Latif SA, Hardy MP, Brem AS. Endogenous inhibitors (GALFs) of 11β- hydroxysteroid dehydrogenase isoforms 1 and 2; derivatives of adrenally produced corticosterone and cortisol. J Steroid Biochem Mol Biol. 2007;4:161–168
  33. Honour JW. The possible involvement of intestinal bacteria in steroidal hypertension. Endocrinology. 1982;110:285–287
  34. Chapman TE, Kraan GP, Nagel GT, Wolthers BG, Drayer NM. Measurement of the cortisol production rate in two sisters with 17α-hydroxylase deficiency using [1,2,3,4–13C] cortisol and isotope dilution mass spectrometry. J Steroid Biochem Mol Biol. 1991;38:489–496
  35. Shackleton CHL, Biglieri EG, Roitman E, Honour JW. Metabolism of radiolabeled coticosterone in an adult with the 17α-hydroxylase deficiency syndrome. J Clin Endocrinol Metab. 1979;48:976–982
  36. Cope CL. Adrenal steroids and disease. In:  Cope CL editors. Metabolic breakdown. London, England: Pitman Medical; 1972;p. 80–104
  37. Rocha R, Stier CT, Kifor I, Ochoa-Maya M, Rennke HG, Williams GH, et al. Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology. 2000;141:3871–3878
  38. Farquharson CA, Struthers AD. Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy. Clin Sci (Lond). 2002;103:425–431

 This study was supported by National Institutes of Health (NIH) Grant HL-52972 and the Lifespan Research Foundation (Dr. Morris) and NIH Grants HL47651, HL59424, DK63214, and a Specialized Center of Research in Molecular Genetics of Hypertension (P50HL055000) from the National Heart, Lung, and Blood Institute. GCRC were supported by Grant M01RR02635 from the National Center for Research Resources, NIH. Dr. Litchfield was in part supported by a NIH Training Grant (T32HL007609).

PII: S1933-1711(08)00003-X

doi: 10.1016/j.jash.2008.01.001

Journal of the American Society of Hypertension
Volume 2, Issue 4 , Pages 286-293 , July 2008