Is there sufficient evidence to consider the use of 11β-hydroxysteroid dehydrogenase type 1 inhibition in children?

Clinical Endocrinology

Volumn 77, Issue 2, 2012, Pages 159-168

  Fürst Recktenwald, Sabine ^a   Dörr, Helmuth G ^b   Quinkler, Marcus ^c   Dötsch, Jörg ^d   Stewart, Paul M ^e  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^d UNIVERSITY OF COLOGNE   (Germany)

^e UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE 1; 3ALPHA(OR 20BETA) HYDROXYSTEROID DEHYDROGENASE; BIOLOGICAL MARKER; CORTICOTROPIN; HYDROCORTISONE; OXIDOREDUCTASE INHIBITOR; SOMATOMEDIN;

BLOOD GLUCOSE MONITORING; BODY COMPOSITION; BODY FAT DISTRIBUTION; BONE AGE; BONE DEVELOPMENT; CELL DIFFERENTIATION; DRUG EFFICACY; DRUG SAFETY; DYSLIPIDEMIA; ENZYME INHIBITION; GLUCOSE HOMEOSTASIS; HORMONE METABOLISM; HUMAN; HYDROCORTISONE RELEASE; HYPERTENSION; IMPAIRED GLUCOSE TOLERANCE; LIPID STORAGE; LIVER METABOLISM; METABOLIC SYNDROME X; NEGATIVE FEEDBACK; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; ONTOGENY; PREPUBERTY; PRIORITY JOURNAL; REVIEW; SEXUAL DEVELOPMENT;

11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1; ADIPOSE TISSUE; ADOLESCENT; CHILD; ENZYME INHIBITORS; HUMANS; HYDROCORTISONE; LIVER; METABOLIC SYNDROME X;

EID: 84863653827     PISSN: 03000664     EISSN: 13652265     Source Type: Journal    
DOI: 10.1111/j.1365-2265.2012.04406.x     Document Type: Review

References (67)

1. Weiss, R., Dziura, J., Burgert, T.S., et al,. (2004) Obesity and the metabolic syndrome in children and adolescents. The New England Journal of Medicine, 350, 2362-2374.
2. Dannemann, A., Ernert, A., Rücker, P., et al,. (2011) Ethnicity and comorbidities in an overweight and obese multiethnic childhood cohort in Berlin. Acta paediatrica, 100, 578-584.
3. Sangun, O., Dündar, B., Kösker, M., et al,. (2011) Prevalence of metabolic syndrome in obese children and adolescents using three different criteria and evaluation of risk factors. Journal of Clinical Research in Paediatric Endocrinology, 3, 70-76.
4. Wei, C., Ford, A., Hunt, L., et al,. (2010) Abnormal liver function in children with metabolic syndrome from a UK-based obesity clinic. Archives of Disease in Childhood, 96, 1003-1007.
5. Schäcke, H., Döcke, W.D., &, Asadullah, K., (2002) Mechanisms involved in the side effects of glucocorticoids. Pharmacology and Therapeutics, 96, 23-43.
6. Paterson, J.M., Morton, N.M., Fievet, C., et al,. (2004) Metabolic syndrome without obesity: hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. Proceedings of the National Academy of Sciences, 101, 7088-7093.
7. Stewart, P.M., Boulton, A., Kumar, S., et al,. (1999) Cortisol metabolism in human obesity: impaired cortisone-cortisol conversion in subjects with central adiposity. Journal of Clinical Endocrinology and Metabolism, 84, 1022-1027.
8. Yang, K., Matthews, S.G., &, Challis, J.R., (1995) Developmental and glucocorticoid regulation of pituitary 11beta-hydroxysteroid dehydrogenase 1 gene expression in the ovine fetus and lamb. Journal of Molecular Endocrinology, 14, 109-116.
9. Gnanalingham, M.G., Mostyn, A., et al,. (2005) Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein-2. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 289, 1407-1415.
10. Stewart, P.M., Whorwood, C.B., &, Mason, J.I., (1995) Type 2 11β-hydroxysteroid dehydrogenase in foetal and adult life. Journal of Steroid Biochemistry and Molecular Biology, 55, 465-471.
11. Phillipov, G., Palermo, M., &, Shackleton, C.H., (1996) Apparent cortisone reductase deficiency: a unique form of hypercortisolism. Journal of Clinical Endocrinology and Metabolism, 81, 3855-3860.
12. Andrew, R., Smith, K., Jones, G.C., et al,. (2002) Distinguishing the activities of 11β-hydroxysteriod dehydrogenasese in vivo using isotopically labeled cortisol. Journal of Clinical Endocrinology and Metabolism, 87, 277-285.
13. Murphy, B.P., (1981) Ontogeny of cortisol-cortisone interconversion in human tissues: a role for cortisone in human fetal development. Journal of Steroid Biochemistry, 14, 811-817.
14. Li, X., Lindquist, S., Chen, R., et al,. (2007) Depot specific messenger RNA expression of 11β-hydroxysteroid dehydrogenase type 1 and leptin in adipose tissue of children and adults. International Journal of Obesity, 31, 820-828.
15. Paulsen, S.K., Pedersen, S.B., JÃ̧rgensen, J.O., et al,. (2006) Growth hormone (GH) substitution in GH-deficient patients inhibits 11beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression in adipose tissue. Journal of Clinical Endocrinology and Metabolism, 91, 1093-1098.
16. Moore, J.S., Monson, J.P., Kaltsas, G., et al,. (1999) Modulation of 11β-hydroxysteroid dehydrogenase isoenzymes by growth hormone and insulin -like growth factor: in vivo and in vitro studies. Journal of Clinical Endocrinology and Metabolism, 84, 4172-4177.
17. Main, K., Philips, M., Joergensen, M., &, Skakkebaek, N.E., (1991) Urinary growth hormone excretion in 657 healthy children and Adults: normal values, inter- and intra-individual variations. Hormone Research, 36, 174-182.
18. Liu, Y.J., Nakagawa, Y., Toya, K., et al,. (1998) Effects of thyroid hormone (thyroxine) and testosterone on hepatic 11β-hydroxysteroid dehydrogenase mRNA and activity in pubertal hypothyroid male rats. Metabolism, 47, 474-477.
19. Dieudonné, M.N., Sammari, A., Dos Santos, E., et al,. (2006) Sex steroids and leptin regulate 11β-hydroxysteroid dehydrogenase I and P450 aromatase expressions in human preadipocytes: sex specificities. Journal of Steroid Biochemistry and Molecular Biology, 99, 189-196.
20. Zhu, L., Hou, M., Sun, B., et al,. (2010) Testosterone stimulates adipose tissue 11β-hydroxysteroid dehydrogenase type 1 expression in a depot-specific manner in children. Journal of Clinical Endocrinology and Metabolism, 95, 3300-3308.
21. Gomez-Sanchez, E.P., Ganjam, V., Chen, Y.J., et al,. (2003) Regulation of 11β-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol. American Journal of Physiology-Endocrinology and Metabolism, 285, E272-E279.
22. Jamieson, P.M., Nyirenda, M.J., Walker, B.R., et al,. (1990) Interactions between oestradiol and glucocorticoid regulatory effects on liver-specific glucocorticoid-inducible genes: possible evidence for a role of hepatic 11β-hydroxysteroid dehydrogenase type 1. Journal of Endocrinology, 160, 103-109.
23. Kushnir, M.M., Blamires, T., Rockwood, A.L., et al,. (2010) Liquid chromatography-tandem mass spectrometry assay for androstenedione, dehydroepiandrosterone, and testosterone with pediatric and adult reference intervals. Clinical Chemistry, 56, 1138-1147.
24. Friedberg, M., Zoumakis, E., Hiroi, N., et al,. (2003) Modulation of 11β-hydroxysteroid dehydrogenase type 1 in mature human subcutaneous adipocytes by hypothalamic messengers. Journal of Clinical Endocrinology and Metabolism, 88, 385-393.
25. Morton, N.M., Holmes, M.C., Fievet, C., et al,. (2001) Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11β-hydroxysteroid dehydrogenase type 1 null mice. Journal of Biological Chemistry, 276, 41293-41300.
26. Seckl, J.R., Morton, N.M., Chapman, K.E., et al,. (2004) Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissue. Recent Progress in Hormone Research, 59, 359-393.
27. Rask, E., Walker, B.R., Söderberg, S., et al,. (2002) Tissue-specific changes in peripheral cortisol metabolism in obese women: increased adipose 11β-hydroxysteroid dehydrogenase type 1 activity. Journal of Clinical Endocrinology and Metabolism, 87, 3330-3336.
28. Mericq, V., Medina, P., Bouwman, C., et al,. (2009) Expression and activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme in subcutaneous and visceral adipose tissue of prepubertal children. Hormone Research, 71, 89-93.
29. Wiegand, S., Richardt, A., Remer, T., et al,. (2007) Reduced 11β-hydroxysteroid dehydrogenase type 1 activity in obese boys. European Journal of Endocrinology, 157, 319-324.
30. Gelernter-Yaniv, L., Feng, N., Sebring, N.G., et al,. (2003) Associations between a polymorphism in the 11 beta hydroxysteroid dehydrogenase type 1 gene and body composition. International Journal of Obesity, 27, 983-986.
31. Quinkler, M., Sinha, B., Tomlinson, J.W., et al,. (2004) Androgen generation in adipose tissue in women with simple obesity-a site-specific role for 17βhydroxysteroid dehydrogenase type 5. Journal of Endocrinology, 183, 331-342.
32. Konopelska, S., Kienitz, T., Hughest, B., et al,. (2009) Hepatic 11beta-HSD1 mRNA expression in fatty liver and nonalcoholic steatohepatitis. Clinical Endocrinology, 70, 554-560.
33. Wudy, A.S., Hartmann, M.F., &, Remer, T., (2007) Sexual dimorphism in cortisol secretion starts after age 10 in healthy children: urinary cortisol metabolite excretion rates during growth. American Journal of Physiology-Endocrinology and Metabolism, 293, E970-E976.
34. Misra, M., Miller, K.K., Almazan, C., et al,. (2004) Alterations in cortisol secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. Journal of Clinical Endocrinology and Metabolism, 89, 4972-4980.
35. Cooper, M.S., Rabbitt, E.H., Goddard, P.E., et al,. (2002) Osteoblastic 11β-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure. Journal of Bone and Mineral Research, 16, 979-986.
36. Justesen, J., Mosekilde, L., Holmes, M., et al,. (2004) Mice deficient in 11β-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation. Endocrinology, 145, 1916-1925.
37. Cooper, M.S., Walker, E.A., Bland, R., et al,. (2000) Expression and functional consequences of 11β-hydroxysteroid dehydrogenase activity in human bone. Bone, 27, 375-381.
38. Lavery, G.G., Walker, E.A., Tiganescu, A., et al,. (2008) Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency. Journal of Clinical Endocrinology and Metabolism, 93, 3827-3832.
39. MaÅunowicz, E.M., Romer, T.E., Urban, M., et al,. (2003) 11beta-hydroxysteroid dehydrogenase type 1 deficiency ('apparent cortisone reductase deficiency') in a 6-year-old boy. Hormone Research, 59, 205-210.
40. Feig, P.U., Shah, S., Hermanowski-Vosatka, A., et al,. (2011) Effect of a 11β-hydroxysteroid dehydrogenase type 1 inhibitor, MK-0916, in patients with type 2 diabetes mellitus and metabolic syndrome. Diabetes, Obesity and Metabolism, 13, 498-504.
41. Rosenstock, J., Banarer, S., Fonseca, V.A., et al,. (2010) The 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy. Diabetes Care, 33, 1516-1522.
42. Rajan, V., Edwards, C.R.W., &, Seckl, J.R., (1996) 11β-Hydroxysteroid dehydrogenase in cultured hippocampal cells reactivates inert 11-dehydrocorticosterone, potentiating neurotoxicity. Journal of Neuroscience, 16, 65-70.
43. Wan, S.L., Liao, M.Y., &, Sun, K., (2002) Postnatal development of 11β-hydroxysteroiod dehydrogenase type 1 in the rat hippocampus. Journal of Neuroscience Research, 69, 681-686.
44. Goodyer, I.M., Park, R.J., Netherton, C.M., et al,. (2001) Possible role for cortisol and dehydroepiandrosterone in human development and psychopathology. British Journal of Psychiatry, 179, 243-249.
45. Maheu, F.S., Merke, D.B., Schroth, E.A., et al,. (2008) Steroid abnormalities and the developing brain: declarative memory for emotionally arousing and neutral material in children with congenital adrenal hyperplasia. Psychoneuroendocrinology, 33, 238-245.
46. Leckie, C.M., Welberg, L.A.M., &, Seckl, J.R., (1998) 11β-Hydroxysteroid dehydrogenase is a predominant reductase in intact rat Leydig cells. Journal of Endocrinology, 159, 233-238.
47. Draper, N., Walker, E.A., Bujalska, I.J., et al,. (2003) Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nature Genetics, 34, 434-439.
48. Jamieson, A., Wallace, A.M., Andrew, R., et al,. (1999) Apparent cortisone reductase deficiency: a functional defect in 11beta-hydroxysteroid dehydrogenase type 1. Journal of Clinical Endocrinology and Metabolism, 84, 3570-3574.
49. Lawson, A.J., Walker, E.A., Lavery, G.G., et al,. (2011) Cortisone-reductase deficiency associated with heterozygous mutations in 11β-hydroxysteroid dehydrogenase type 1. Proceedings of the National Academy of Sciences, 108, 4111-4116.
50. Dötsch, J., Hohenberger, I., Peter, M., et al,. (2000) Evidence for change of 11β-hydroxysteroid dehydrogenase activity during infancy and childhood. Paediatric Research, 48, 697-700.
51. Dimitriou, T., Mase-Gluth, C., &, Remer, T., (2003) Adrenocorticoal activity in healthy children is associated with fat mass. American Journal of Clinical Nutrition, 77, 731-736.
52. Andrews, R.C., Herlihy, O., Livingstone, D.E., et al,. (2002) Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance. Journal of Clinical Endocrinology and Metabolism, 87, 5587-5593.
53. Bujalska, I.J., Quinkler, M., Tomlinson, J.W., et al,. (2006) Expression profiling of 11β-hydroxysteroid dehydrogenase type-1 and glucocorticoid-target genes in subcutaneous and omental human preadipocytes. Journal of Molecular Endocrinology, 37, 327-340.
54. Hammami, M.M., &, Siiteri, P.K., (1991) Regulation of 11b-hydroxysteroid dehydrogenase activity in human skin fibroblasts: enzymatic modulation of glucocorticoid action. Journal of Clinical Endocrinology and Metabolism, 73, 326-334.
55. Knutsson, U., Dahlgren, J., Marcus, C., et al,. (1997) Circadian cortisol rhythms in healthy boys and girls: relationship with age, growth, body composition, and pubertal development. Journal of Clinical Endocrinology and Metabolism, 82, 536-540.
56. Kiess, W., Meidert, A., Dressendörfer, R.A., et al,. (1995) Salivary cortisol levels throughout childhood and adolescence: relation with age, pubertal stage, and weight. Pediatric Research 37, 502-6.
57. Reinehr, T., &, Andler, W., (2004) Cortisol and its relation to insulin resistance before and after weight loss in obese children. Hormone Research, 62, 107-112.
58. Courtney, R., Stewart, P.M., Toh, M., et al,. (2008) Modulation of 11β-hydroxysteroid dehydrogenase (11βHSD) activity biomarkers and pharmacokinetics of PF-00915275, a selective 11βHSD1 inhibitor. Journal of Clinical Endocrinology and Metabolism, 93, 550-556.
59. Tomlinson, J.W., Finney, J., Hughes, B.A., et al,. (2008) Reduced glucocorticoid production rate, decreased 5α-reductase activity, and adipose tissue insulin sensitization after weight loss. Diabetes, 57, 1-8.
60. Basu, R., Basu, A., Grudzien, M., et al,. (2009) Liver is the site of splanchnic cortisol production in obese nondiabetic humans. Diabetes, 58, 39-45.
61. Edgerton, D.S., Basu, R., Ramnanan, C.J., et al,. (2010) Effect of 11 beta-hydroxysteroid dehydrogenase-1 inhibition on hepatic glucose metabolism in the conscious dog. American Journal of Physiology-Endocrinology and Metabolism, 298, E1019-1026.
62. Shi, L., Wudy, S.A., Maser-Gluth, C., et al,. (2011) Urine volume dependency of specific dehydroepiandrosterone (DHEA) and cortisol metabolites in healthy children. Steroids, 76, 140-144.
63. Yamada, J., Stevens, B., de Silva, N., et al,. (2007) Hair cortisol as a potential biologic marker of chronic stress in hospitalized neonates. Neonatology, 92, 42-49.
64. Raul, J.S., Cirimele, V., Ludes, B., et al,. (2004) Detection of physiological concentrations of cortisol and cortisone in human hair. Clinical Biochemistry, 37, 1105-1111.
65. Gibbs, J.P., Emery, M.G., McCafferey, I., et al,. (2010) Population pharmacokinetic/pharmacodynamic model of subcutaneous adipose 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity after oral administration of AMG 221, a selective 11β-HSD1 inhibitor. Journal of Clinical Pharmacology, 51, 830-841.
66. Shah, S., Hermanowski-Vosatka, A., Gibson, K., et al,. (2011) Efficacy and safety of selective 11β-HSD-1 inhibitors MK-0736 and MK-0916 in overweight and obese patients with hypertension. Journal of American Society of Hypertension, 5, 166-176.
67. Fuerst-Recktenwald, S., Abt, M., &, Arlt, W., (2011) Effects of two 11β-HSD1 inhibitors on the hypothalamo-pituitary-adrenal axis of male and female type 2 diabetic patients. Endocrine Reviews, 32, Meeting Abstracts: OR39-44.