IJCM  Vol.3 No.4 , July 2012
Regulation of 11β-Hydroxysteroid Dehydrogenase Type 1 and 2 in Rheumatoid Arthritis
ABSTRACT
Objective. The sequential activities of the 11β-hydroxysteroid dehydrogenase enzymes type 1 and 2 have not been investigated so far in patients suffering from rheumatoid arthritis before and after starting treatment though the enzymes balancing cortisol and cortisone levels are involved in regulating various inflammatory diseases. Methods. In a retrospective study, a panel of 41 urinary steroid metabolites has been analysed in a group of 18 patients with active rheumatoid arthritis (RA) as they were brought under control with disease modifying drugs. Results. No major changes were found in a variety of androgen, oestrogen and progesterone metabolites, however the ratio of THF + 5αTHF/THE as an index of 11β-HSD1 oxidative activity demonstrated down-regulation with modification correlating significantly with change in acute phase reactants as the disease came under control. These findings were supported by a tendency of a reduced ratio of F/E, an index of 11β-HSD2 oxidative activity, resulting in a significant correlation of the two ratios (p < 0.001). This parallelism of the two enzymes with functions of clinical laboratory parameters during drug-induced improvement of the disease is novel. Conclusions. Urinary steroid metabolites, which alter with disease activity, may provide further insight into the mechanisms by which stress can modify arthritis through hormones.

Cite this paper
C. Beyeler, B. Dick, H. A. Bird and B. M. Frey, "Regulation of 11β-Hydroxysteroid Dehydrogenase Type 1 and 2 in Rheumatoid Arthritis," International Journal of Clinical Medicine, Vol. 3 No. 4, 2012, pp. 254-262. doi: 10.4236/ijcm.2012.34051.
References
[1]   M. Vogeser, R. Zachoval, T. W. Felbinger and K. Jacob, “Increased Ratio of Serum Cortisol to Cortisone in Acute-Phase Response,” Hormone Research, Vol. 58, No. 4, 2002, pp. 172-175. doi:10.1159/000065486

[2]   K. E. Chapman, A. Coutinho, M. Gray, J. S. Gilmour, J. S. Savill and J. R. Seckl, “Local Amplification of Glucocorticoids by 11beta-Hydroxysteroid Dehydrogenase Type 1 and Its Role in the Inflammatory Response,” Annals of the New York Academy of Sciences, Vol. 1088, 2006, pp. 265-273. doi:10.1196/annals.1366.030

[3]   K. Raza, R. Hardy and M. S. Cooper, “The 11beta-Hydroxysteroid Dehydrogenase Enzymes—Arbiters of the Effects of Glucocorticoids in Synovium and Bone,” Rheumatology, Vol. 49, No. 11, 2010, pp. 2016- 2023. doi:10.1093/rheumatology/keq212

[4]   Z. Hochberg, M. Friedberg, L. Yaniv, T. Bader and D. Tiosano, “Hypotha-lamic Regulation of Adiposity: The Role of 11beta-Hydroxysteroid Dehydrogenase Type 1,” Hormone and Metabolic Research, Vol. 36, No. 6, 2004, pp. 365-369. doi:10.1055/s-2004-814570

[5]   C. D. Heiniger, M. K. Rochat, F. J. Frey and B. M. Frey, “TNF-Alpha Enhances Intracellular Glucocorticoid Avai- lability,” Federation of European Biochemical Societies Letters, Vol. 507, No. 3, 2001, pp. 351-356. doi:10.1016/S0014-5793(01)03004-6

[6]   R. M. Kosta-dinova, A. R. Nawrocki, F. J. Frey and B. M. Frey, “Tumor Necrosis Factor Alpha and Phorbol 12-Myristate-13-Acetate Down-Regulate Human 11beta-hydroxysteroid Dehydrogenase Type 2 through p50/p50 NF-KappaB Homodimers and Egr-1,” Federation of American Societies for Experimental Biology Journal, Vol. 19, No. 6, 2005, pp. 650-652.

[7]   G. Escher, I. Galli, B. S. Vishwanath, B. M. Frey and F. J. Frey, “Tumor Necrosis Factor Alpha and Interleukin 1beta Enhance the Cortisone/Cortisol Shuttle,” Journal of Experimental Medicine, Vol. 186, No. 2, 1997, pp. 189- 198. doi:10.1084/jem.186.2.189

[8]   Z. Krozowski and Z. Chai, “The Role of 11beta-Hydroxysteroid Dehydroge-nases in the Cardiovascular System,” Endocrinology Journal, Vol. 50, No. 5, 2003, pp. 485-489.

[9]   B. E. Orsida, Z. S. Krozowski and E. H. Walters, “Clinical Re-levance of Airway 11beta-Hydroxysteroid Dehydrogenase Type II Enzyme in Asthma,” American Journal of Respiratory Critical Care Medicine, Vol. 165, No. 7, 2002, pp. 1010-1014.

[10]   K. I. Takahashi, K. Fukushima and H. Sasano, “Type II 11beta-Hydroxysteroid De-hydrogenase Expression in Human Colonic Epithelial Cells of Inflammatory Bowel Disease,” Digestive Diseases and Sciences, Vol. 44, No. 12, 1999, pp. 2516-2522. doi:10.1023/A:1026699324927

[11]   D. Fuster, G. Escher, B. Vogt and F. J. Frey, “Furosemide Inhibits 11beta-Hydroxysteroid Dehydrogenase Type 2,” Endo-crinology, Vol. 139, No. 9,1998, pp. 3849-3854. doi:10.1210/en.139.9.3849

[12]   J. W. Tomlinson and P. M. Stewart, “Cortisol Metabolism and the Role of 11beta-Hydroxysteroid Dehydrogenase,” Best Practice & Research Clinical Endocrinology & Metabolism, Vol. 15, No. 1, 2001, pp. 61-78. doi:10.1053/beem.2000.0119

[13]   C. Beyeler, B. M. Frey and H. A. Bird, “Urinary 6 Beta-Hydroxycortisol Excretion in Rheumatoid Arthritis,” British Journal of Rheumatology, Vol. 36, No. 1, 1997, pp. 540-58. doi:10.1093/rheumatology/36.1.54

[14]   M. Schmidt, C. Weidler, H. Naumann, S. Anders, J. Scholmerich and R. H. Straub, “Reduced Capacity for the Reactivation of Glucocorticoids in Rheumatoid Arthritis Synovial Cells: Possible Role of the Sympathetic Nervous System?” Arthritis Rheumatism, Vol. 52, No. 6, 2005, pp. 1711-1720. doi:10.1002/art.21091

[15]   F. C. Arnett, S. M. Edworthy and D. A. Bloch, “The American Rheumatism Association 1987 Revised Criteria for the Classification of Rheumatoid Arthritis,” Arthritis Rheumatism, Vol. 31, No. 3, 1988, pp. 315-324. doi:10.1002/art.1780310302

[16]   U. Islander, C. Jochems, M. K. Lagerquist, H. Forsblad-d’Elia and H. Carlsten, “Estrogens in Rheumatoid Arthritis; The Immune System and Bone,” Molecular Cellular Endocrinology, Vol. 335, No. 1, 2011, pp. 14- 29. doi:10.1016/j.mce.2010.05.018

[17]   D. M. Ritchie, J. A. Boyle and J. M. McInnes, “Clinical Studies with an Arti-cular Index for the Assessment of Joint Tenderness in Pa-tients with Rheumatoid Arthritis,” Quaterly Journal of Medicine, Vol. 37, No. 147, 1968, pp. 393-406.

[18]   C. Beyeler, A. K. Daly, M. Armstrong, C. Astbury, H. A. Bird and J. R. Idle, “Phenotype/Genotype Relationships for the Cytochrome P450 Enzyme CYP2D6 in Rheuma-toid Arthritis: Influence of Drug Therapy and Disease Activity,” Journal of Rheumatoly, Vol. 21, No. 6, 1994, pp. 1034-1039.

[19]   C. Quattropani, B. Vogt, A. Odermatt, B. Dick, B. M. Frey and F. J. Frey, “Reduced Activity of 11 Beta-Hydroxysteroid Dehydrogenase in Patients with Cholestasis,” Journal Clinical Investigation, Vol. 108, No. 9, 2001, pp. 1299-1305.

[20]   B. Kirkwood, “Essentials of Medical Statistics,” Wiley-Blackwell, New York, 2003.

[21]   M. L. Licketts and P. M. Stewart, “Regulation of 11Beta-Hydroxysteroid Dehydrogenase Type 2 by Diuretics and the Renin-Angiotensin-Aldosterone Axis,” Clinical Science, Vol. 96, No. 6, 1999, pp. 669-675.

[22]   M. Quinkler, D. Zehnder and J. Lepenies, “Expression of Renal 11beta-Hydroxysteroid Dehydrogenase Type 2 Is Decreased in Patients with Impaired Renal Function,” European Journal of Endocrinology, Vol. 153, No. 2, 2005, pp. 291-299. doi:10.1530/eje.1.01954

[23]   E. A. Walker, A. Ahmed and G. G. Lavery, “11Beta- Hydroxysteroid Dehydrogenase Type 1 Regulation by Intracellular Glucose 6-Phosphate Provides Evidence for a Novel Link between Glucose Metabolism and Hypothalamo-Pituitary-Adrenal Axis Function,” Journal of Biological Chemistry, Vol. 282, No. 37, 2007, pp. 27030- 27036. doi:10.1074/jbc.M704144200

[24]   B. H. Scott, “Auto-Immunity and Connective Tissue Disorders,” Oxford Medical Publications, Oxford University Press, Oxford, 1990.

[25]   M. Cutolo, B. Seriolo, C. Craviotto, C. Piz-zorni and A. Sulli, “Circadian Rhythms in RA,” Annals of the Rheumatic Diseases, Vol. 62, No. 7, 2003, pp. 593-596. doi:10.1136/ard.62.7.593

[26]   A. K. Bhall, “Hormones and the Immune Response,” Annals of the Rheumatic Diseases, Vol. 48, No. 1, 1989, pp. 1-6. doi:10.1136/ard.48.1.1

[27]   B. W. Kirkham and G. S. Panayi, “Diurnal Periodicity of Cortisol Secretion, Immune Reactivity and Disease Activity in Rheumatoid Arthritis: Implications for Steroid Treatment,” British Journal of Rheumatology, Vol. 28, No. 2, 1989, pp. 154-157. doi:10.1093/rheumatology/28.2.154

[28]   N. Bellamy, R. B. Sothern, J. Campbell and W. W. Buchanan, “Circadian Rhythm in Pain, Stiffness, and Manual Dexterity in Rheumatoid Arthritis: Relation between Discomfort and Disability,” Annals of the Rheumatic Diseases, Vol. 50, No. 4, 1991, pp. 243-248. doi:10.1136/ard.50.4.243

[29]   S. Bombardieri, A. Clerico, L. Riente, M. G. Del Chicca and C. Vitali, “Circadian Variations of Serum Myoglobin Levels in Normal Subjects and Patients with Polymyositis,” Arthritis Rheumatism, Vol. 25, No. 12, 1982, pp. 1419-1424. doi:10.1002/art.1780251205

[30]   M. G. Perry, J. R. Kirwan, D. S. Jessop and L. P. Hunt, “Overnight Variations in Cortisol, Interleukin 6, Tumour Necrosis Factor Alpha and Other Cytokines in People with Rheumatoid Arthritis,” Annals of the Rheumatic Diseases, Vol. 68, No. 1, 2009, pp. 63-68. doi:10.1136/ard.2007.086561

[31]   M. Cutolo, “Androgens in Rheumatoid Arthritis: When Are They Effectors?” Arthritis Research & Therapy, Vol. 11, No. 5, 2009, p. 126. doi:10.1186/ar2804

[32]   A. Martocchia, M. Stefanelli, S. Cola and P. Falaschi, “Sex Steroids in Autoimmune Diseases,” Current Topics in Medicinal Chemistry, Vol. 11, No. 13, 2011, pp. 1668-1683. doi:10.2174/156802611796117595

[33]   M. Cutolo, B. Villaggio, C. Craviotto, C. Pizzorni, B. Seriolo and A. Sulli, “Sex Hormones and Rheumatoid Arthritis,” Autoimmunity Reviews, Vol. 1, No. 5, 2002, pp. 284-289. doi:10.1016/S1568-9972(02)00064-2

[34]   A. Gupta and A. J. Silman, “Psychological Stress and Fibromyalgia: A Review of the Evidence Suggesting a Neuroendocrine Link,” Arthritis Research & Therapy, Vol. 6, No. 3, 2004, pp. 98-106. doi:10.1186/ar1176

[35]   R. H. Straub, F. S. Dhabhar, J. W. Bijlsma and M. Cutolo, “How Psychological Stress via Hormones and Nerve Fibers May Exacerbate Rheumatoid Arthritis,” Arthritis Rheumatism, Vol. 52, No. 1, 2005, pp. 16-26. doi:10.1002/art.20747

[36]   F. Buttgereit, H. Zhou and M. J. Seibel, “Arthritis and Endogenous Glucocorticoids: The Emerging Role of the 11Beta-HSD Enzymes,” Annals of the Rheumatic Diseases, Vol. 67, No. 9, 2008, pp. 1201-1203. doi:10.1136/ard.2008.092502

[37]   R. Hardy, E. H. Rab-bitt and A. Filer, “Local and Systemic Glucocorticoid Metabolism in Inflammatory Arthritis,” Annals of the Rheumatic Diseases, Vol. 67, No. 9, 2008, pp. 1204-1210. doi:10.1136/ard.2008.090662

 
 
Top