11β-hydroxysteroid dehydrogenase Type 1 as a novel therapeutic target in metabolic and neurodegenerative disease

Expert Opinion on Therapeutic Targets

Volumn 7, Issue 6, 2003, Pages 771-783

  Walker, Brian R ^a   Seckl, Jonathan R ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

11 hydroxysteroid dehydrogenase Type 1 (11HSD1); Cognitive impairment no dementia; Glucocorticoids; Hypertension; Metabolic syndrome

Indexed keywords

11 HYDROXYCORTICOSTEROID; 11ALPHA HYDROXYPROGESTERONE; 11BETA HYDROXYPROGESTERONE; 11BETA HYDROXYSTEROID DEHYDROGENASE; 11BETA HYDROXYSTEROID DEHYDROGENASE INHIBITOR; BIOFLAVONOID; CARBENOXOLONE; CHENODEOXYCHOLIC ACID; CHOLIC ACID; CORTICOSTERONE DERIVATIVE; CORTISONE; DEHYDROCORTICOSTERONE; EPIHYDROCORTISONE; FINASTERIDE; FUROSEMIDE; GLUCOCORTICOID; GLYCYRRHETINIC ACID; GLYCYRRHIZIC ACID; GOSSYPOL; KETOCONAZOLE; LETROZOLE; METYRAPONE; MIFEPRISTONE; OXIDOREDUCTASE INHIBITOR; PREDNISOLONE DERIVATIVE; PROGESTERONE DERIVATIVE; SAIBOKU TO; TETRAHYDROPROGESTERONE; THIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ENZYME INHIBITOR; GLUCOCORTICOID RECEPTOR; HYDROCORTISONE;

ADIPOSE TISSUE; AGING; BRAIN TISSUE; CATALYSIS; CELL LEVEL; COGNITIVE DEFECT; CORTICOSTEROID BLOOD LEVEL; CUSHING SYNDROME; DEGENERATIVE DISEASE; DRUG MECHANISM; DRUG PENETRATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HYPERADRENOCORTICISM; HYPERANDROGENISM; LIVER PARENCHYMA; METABOLIC DISORDER; METABOLITE; NONHUMAN; OBESITY; PATHOGENESIS; REVIEW; STRESS; TRANSGENIC MOUSE; ANIMAL; BLOOD; DRUG ANTAGONISM; DRUG EFFECT; ENZYMOLOGY; FEMALE; GENETICS; HYPOPHYSIS ADRENAL SYSTEM; HYPOTHALAMUS HYPOPHYSIS SYSTEM; MALE; METABOLIC SYNDROME X; METABOLISM; MOUSE; MOUSE MUTANT; PATHOPHYSIOLOGY; PHYSIOLOGY; RAT; SECRETION; ZUCKER RAT;

11-BETA-HYDROXYSTEROID DEHYDROGENASES; ADIPOSE TISSUE; ANIMALS; CUSHING SYNDROME; ENZYME INHIBITORS; FEMALE; GLUCOCORTICOIDS; GLYCYRRHETINIC ACID; HUMANS; HYDROCORTISONE; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; MALE; METABOLIC SYNDROME X; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; NEURODEGENERATIVE DISEASES; OBESITY; PITUITARY-ADRENAL SYSTEM; RATS; RATS, ZUCKER; RECEPTORS, GLUCOCORTICOID;

EID: 85047691378     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.7.6.771     Document Type: Review

References (136)

1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adult, (Adult Treatment Panel III). JAMA (2001) 285:2486-2497.
2. ETXABE J, VAZQUEZ JA: Morbidity and mortality in Cushing's disease: an epidemiological approach Clin. Endocrinol. (1994) 40:479-484.
3. COLAO A, PIVONELLO R, SPIEZIA S et al.: Persistence of increased cardiovascular risk in patients with Cushing's disease after five years of successful cure. J. Clin. Endocrinol. Metab. (1999) 84:2664-2672.
4. REUS VI, WOLKOWITZ OM: Antiglucocorticoid drugs in the treatment of depression. Expert Opin. Invest. Drugs (2001) 10:1789-1796.
5. BJORNTORP P, HOLM G, ROSMOND R: Hypothalamic arousal, insulin resistance and Type 2 diabetes mellitus. Diabetic Med. (1999) 16:373-381.
6. FILIPOVSKY J, DUCIMETIERE P, ESCHWEGE E, RICHARD JL, ROSSELIN G, CLAUDE JR: The relationship of blood pressure with glucose, insulin, heart rate, free fatty acids and plasma cortisol levels according to degree of obesity in middle-aged men. J. Hypertens. (1996) 14:229-235.
7. WALKER BR, PHILLIPS DI, NOON JP et al.: Increased glucocorticoid activity in men with cardiovascular risk factors. Hypertension (1998) 31:891-895.
8. FRASER R, INGRAM MC, ANDERSON NH, MORRISON C DAVIES E, CONNELL JM: Cortisol effects on body mass, blood pressure, and cholesterol in the general population. Hypertension (1999) 33:1364-1368.
9. LUPIEN SJ, DE LEON M, DE SANTI S et al.: Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat. Neurosci. (1998) 1:69-73.
10. WOLKOWITZ OM, REUSVI, CHAN T et al.: Antiglucocorticoid treatment of depression: double-blind ketoconazole. Biol. Psych. (1999) 45:1070-1074.
11. GAILLARD RC, POFFET D, RIONDEL AM, SAURAT JH: RU486 inhibits peripheral effects of glucocorticoids; in humans. J Clin. Endocrinol. Metab. (1985) 61:1009-1011.
12. ELMORE SW, COGHLAN MJ, ANDERSON DD et al.: Nonsteroidal selective glucocorticoid modulators: the effect of C-5 alkyl substitution on the transcriptional activation/repression profile of 2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1] benzopyrano[3,4-f]quinotines. J. Med. Chem. (2001) 44:4481-4491.
13. COGHLAN MJ, JACOBSON PB, LANE B et al.: A novel anti-inflammatory maintains glucocorticoid efficacy with reduced side effects. Mol. Endocrinol. (2003) 17:860-869.
14. KYM PR, KORT ME, COGHLAN MJ et al.: Nonsteroidal selective glucocorticoid modulators: die effect of C-10 substitution on receptor selectivity and functional potency of 5-allyl-2,5-dihydro-2,2,4-trimethyl-1h-[1] benzopyrano[3,4-f]quinolines. J. Med. Chem (2003) 46:1016-1030.
15. EDGERTON D, SCOTT M, DOSS N et al.: A liver-selective glucocorticoid receptor antagonist (A-348441) inhibits net hepatic glucose output in the fasted dog. Diabetes (2003) 52(Suppl. 1)-A118. Abstract.
16. STEWART PM, SHEPPARD MC: Novel aspects of hormone action: intracellular ligand supply and its control by a series of tissue specific enzymes. Mol. Cell. Endocrinol, (1992) 83:C13-C18.
17. SECKL JR, WALKER BR (Eds): Bailliere's Best Practice and Reasearch in Clinical Endocrinolgy and Metabolism - Disorders of Steroid Metabolism Bailliere Tindall, London (2001).
18. (+)-dependent isoform of 11β-hydroxysteroid dehydrogenase. Cloning and characterisation of cDNA from sheep kidney. J. Biol. Chem. (1994) 269:25959-25962.
19. ALBISTON AL, OBEYESEKERE VR, SMITH RE, KROZOWSKI ZS: Cloning and tissue distribution of the human 11β-hydroxysteroid dehydrogenase Type 2 enzyme. Mol. Cell. Endocrinol. (1994) 105:R11-R17.
20. STEWART PM, KROZOWSKI ZS: 11β-Hydroxysteroid dehydrogenase. Vitam. Horm. (1999) 57:249-324.
21. WILSON RC, HARBISON MD, KROZOWSKI ZS et al.: Several homozygous mutations in the gene for 11β-hydroxystemid dehydrogenase Type 2 in patients with apparent mineralocorticoid excess. J. Clin. Endocrinol. Metab. (1995) 80:3145-3150.
22. MONDER C, STEWART PM, LAKSHMI V, VALENTINO R, BURT D, EDWARDS CR. Licorice inhibits corticosteroid 11β-dehydrogenase of rat kidney and liver: in vivo and in vitro studies. Endocrinology (1989) 125:1046-1053.
23. KOTELEVTSEV YV, BROWN RW, FLEMING S, EDWARDS CR, SECKL JR, MULLINS JJ: Hypertension in mice caused by inactivation of 11β-hydroxysteroid dehydrogenase Type 2. J. Clin. Invest. (1999) 103:683-689.
24. BROWN RW, DIAZ R, ROBSON AC et al.: The ontogeny of 11β-hydroxysteroid dehydrogenase Type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Endocriology (1996) 137:794-797.
25. STEWART PM, ROGERSON FM, MASON JI: Type 2 11β-hydroxysteroid dehydrogenase messenger RNA and activity in human placenta and fecal membranes: its relationship to birth weight and putative role in fetal steroidogenesis. J. Clin. Endocrinol. Metab. (1995) 80:885-890.
26. CHRISTY C, HADOKE PW, PATERSON JM, MULLINS JJ, SECKL JR, WALKER BR: Glucocorticoid action in mouse aorta; localisation of 11β-hydroxysteroid dehydrogenaseType 2 and effects on responses to glucocorticoids in vitro. Hypertension (2003) 42:580-587.
27. YONG PYK, THONG KJ, ANDREW R, WALKER BR, HILLIER SG: Development-related increase in cortisol biosynthesis by human granulosa cells. J. Clin. Endocrinol, Metab. (2000) 85:4728-4733.
28. AGARWAL AK, MONDER C, ECKSTEIN B, WHITE PC: Cloning and expression of rat cDNA encoding corticosteroid 11β-dehydrogenase. J. Biol. Chem. (1989) 264:18939-18943.
29. SECKL JR, WALKER BR. Minireview: 11β-hydroxysreroid dehydrogenase Type 1 - a tissue-specific amplifier of glucocorticoid action. Endocrinology (2001) 142:1371-1376.
30. LOW SC, CHAPMAN KE, EDWARDS CR, SECKL JR. 'Liver-type' 11β-hydroxysteroid dehydrogenase cDNA encodes reductase but not dehydrogenase activity in intact mammalian COS-7 cells. J. Mol. Endocrinol. (1994) 13:167-174.
31. BUJALSKA IJ, KUMAR S, STEWART PM: Does central obesity reflect 'Cushing's disease of die omentum'? Lancet (1997) 349:1210-1213.
32. JAMIESON PM, CHAPMAN KE, EDWARDS CR, SECKL JR. 11β-Hydroxysteroid dehydrogenase is an exclusive 11β-reductase in primary cultures of rat hepatocytes: effect of physicochemical and hormonal manipulations. Endocrinology (1995) 136:4754-4761.
33. RAJAN V, EDWARDS CR, SECKL JR. β-Hydroxysteroid dehydrogenase in cultured hippocampal cells reactivates inert 11-dehydrocorticosterone, potentiating neurotoxicity. J. Neurosci. (1996) 16:65-70.
34. JAMIESON PM, WALKER BR, CHAPMAN KE, ROSSITER S, SECKL JR: 11β-Hydroxysteroid dehydrogenase Type 1 is a predominant 11-reductase in the intact perfused rat liver. J. Endocrinol. (2000) 175:685-692.
35. WALKER BR, CAMPBELL JC, FRASER R, STEWART PM, EDWARDS CR. Mineralocorticoid excess and inhibition of 11β-hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome. Clin. Endocrinol. (Oxf.) (1992) 37:483-492.
36. KATZ JR, MOHAMED-ALI V, WOOD PJ, YUDKIN JS, COPPACK SW: An in vivo study of the cortisol - cortisone shuttle in subcutaneous abdominal adipose tissue. Clin. Endocrinol. (1999) 50:63-68.
37. PHILLIPS DM, LAKSHMI V. MONDER C: Corticosteroid 11β-dehydrogenase in rat testis. Endocrinology (1989) 125:209-216.
38. BUJALSKA IJ, WALKER EA. HEWISON M, STEWART PM: A switch in dehydrogenase to reductase activity of 11β-hydroxysteroid dehydrogenase Type 1 upon differentiation of human omental adipose stromal cells. J. Clin. Endocrinol. Metab. (2002) 87:1205-1210.
39. DRAPER N, WALKER EA, BUJALSKA IJ et al.: Mutations in the genes encoding 11β-hydroxysteroid dehydrogenase Type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat. Genet. (2003) 34:434-439.
40. MASER E, VOLKER B, FRIEBERTSHAUSER J: 11β-Hydroxysteroid dehydrogenase Type 1 from human liver: dimerization and enzyme cooperativity support its postulated role as glucocorticoid reductase. Biochemistry (2002) 41:2459-2465.
41. SHAFQAT N, ELLEBY B, SVENSSON S et al.: Comparative enzymology of 11β-hydroxysteroid dehydrogenase Type 1 from glucocorticoid resistant (guinea pig) versus sensitive (human) species. J. Biol. Chem. (2003) 278:2030-2035.
42. RABBITT EH, LAVERY GG, WALKER EA, COOPER MS, STEWART PM, HEWISON M: Prereceptor regulation of glucccorticoid action by 11 [β]-hydroxysteroid dehydrogenase: a novel determinant of cell proliferation. FASEB J. (2002) 16:36-44.
43. BUJALSKA IJ, KUMAR S, HEWISON M, STEWART PM: Differentiation of adipose stromal cells: the roles of glucocorticoids and 11β-hydroxysteroid dehydrogenase. Endocrinology (1999) 140:3188-3196.
44. YANG K, KHALIL MW, STRUTT BJ, KILLINGER DW. 11β-Hydroxysteroid dehydrogenase 1 activity and gene expression in human adipose stromal cells: effect on aromatase activity. J. Steroid Biochem. Mol. Biol. (1997) 60:247-253.
45. MASUZAKI H, PATERSON J, SHINYAMA H et al.: A transgenic model of visceral obesity and the metabolic syndrome. Science (2001) 294:2166-2170.
46. PATERSON JM, HOLMES MC, MORTON NM, SECKL JR, MULLINS JJ: Liver-specific over-expression of 11β-HSD1 in transgenic mice produces insulin resistance, hyperlipidaemia and fatty liver. Proc. Endo. 2002 (2002) P2-319. Abstract.
47. KOTELEVTSEV YV, HOLMES MC, BURCHELL A et al.: 11β-Hydroxysteroid dehydrogenase Type 1 knockout mice show attenuated glucocorticoid inducible responses and resist hyperglycaemia on obesity and sum. Proc. Natl. Acad. Sci USA (1997) 94:14924-14929.
48. HARRIS HJ, KOTELEVTSEV YV, MULLINS JJ, SECKL JR, HOLMES MC: 11β-Hydroxysteroid dehydrogenaseType 1 null mice have altered hypothalamic-pituitary-adrenal axis activity: a novel control of glucocorticoid feedback. Endocrinology (2001) 142:114-120.
49. MORTON NM, HOLMES MC, FIEVET C et al.: Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11β-hydroxysteroid dehydrogcnase Type 1 null mice. J. Biol. Chem. (2001) 276:41293-41300.
50. MORTON NM, PATERSON JM, HOLMES MC, WALKER BR, MULLINS JJ, SECKL JR: 11β-Hydroxysteroid dehydrogenase Type 1 null mice resist dietary obesity and its metabolic complications. Proc. Endo. 2002 (2002) OR17-3. Abstract.
51. MASUZAKI H, YAMAMOTO H, KENYON CJ et al.: Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. J. Clin. Invest. (2003) 112:83-90.
52. PATERSON JM, MORTON NM, HOLMES MC et al.: Metabolic syndrome without obesity-liver-specific overexpression of 11β-HSD1 in transgenic mice. Proc. Endo. 2003 (2003) OR39-4. Abstract.
53. YAU JL, NOBLE JM, KENYON CJ et al.: Lack of tissue glucocorticoid reactivation in 11β-hydroxysteroid dehydrogenase Type 1 knockout mice ameliorates age-related learning impairments. Proc. Natl. Acad. Sci. USA (2001) 98:4716-4721.
54. RITCHIE K, TOUCHON J: Mild cognitive impairment: conceptual basis and current nosological status. Lancet (2000) 355:225-228.
55. LJUNG T, ANDERSSON B, BENGTSSON B, BJORNTORP P, MARIN P: Inhibition of cortisol secretion by dexamethasone in relation to body fat distribution: a dose-response study. Obes. Res. (1996) 4:277-282.
56. WALKER B, SODERBERG S, LINDAHL B, OLSSON T: Independent effects of obesity and cortisol in predicting cardiovascular risk factors in men and women. J. Intern. Med. (2000) 247:198-204.
57. ROSMOND R, DALLMAN MF, BJORNTORP P: Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and haemodynamic abnormalities. J. Clin. Endocrinol. Metab. (1998) 83:1853-1859.
58. STRAIN GW, ZUMOFF B, STRAIN JJ, LEVIN J, FUKUSHIMA DK: Cortisol production in obesity. Metabolism (1980) 29:980-985.
59. LOTTENBERG SA. GIANNELLA-NETO D, DERENDORF H et al.: Effect of fat distribution on the pharmacokinetics of cortisol in obesity. Int. J. Clin. Pharmacol. Ther. (1998) 36:501-505.
60. ANDREW R, PHILLIPS DI, WALKER BR: Obesity and gender influence cortisol secretion and metabolism in man. J. Clin. Endocrinol. Metab. (1998) 83:1806-1809.
61. REYNOLDS RM, WALKER BR, PHILLIPS DI et al.: Altered control of cortisol secretion in adult men with low birthweight and cardiovascular risk factors. J. Clin. Endorinol. Metab. (2001) 86:245-250.
62. WALKER BR: How will we know if 11β-hydroxysteroid dehydrogenases are important in common diseases? Clin. Endocrinol. (Oxf.) (2000) 52:401-402.
63. STEWART PM, WALLACE AM, ATHERDEN SM, SHEARING CH, EDWARDS CR: Mineralocorticoid activity of cathenoxolone: contrasting effects of carbenoxolone and liquorice on 11β-hydroxysteroid dehydrogenase activity in man. Clin. Sci. (1990) 78:49-54.
64. RASK E, WALKER BR, SODERBERG S et al.: Tissue-specific changes in peripheral cortisol metabolism in obese women: increased adipose 11β-hydroxysteroid dehydrogenase Type 1 activity. J. Clin. Endocrinol. Metab. (2002) 87:3330-3336.
65. TIOSANO D, EISENTEIN I, MILITIANU D, CHROUSOS GP, HOCHBERG Z: 11β-Hydroxysteroid dehydrogenase activity in hypothalamic obesity. J. Clin. Endocrinol. Metab. (2003) 88:379-384.
66. STEWART PM, BOULTON A, KUMAR S, CLARK PM, SHACKLETON CH: Cortisol metabolism in human obesity: impaired cortisone-cortisol conversion in subjects with central adiposity. J. Clin Endocrinol. Metab. (1999) 84:1022-1027.
67. RASK E, OLSSON T, SODERBERG S et al.: Tissue-specific dysregulation of cortisol metabolism in human obesity. J. Clin. Endocrinol. Metab. (2001) 86:1418-1421.
68. WESTERBACKA J, YKI-JARVINEN H, VEHKAVAARA S et al.: Body fat distribution and cortisol metabolism in healthy men: enhanced 5β-reductase and lower cortisol/cortisone metabolite ratios in men with fatty liver. J. Clin. Endocrinol. Metab. (2003) 88:4924-4931.
69. LIVINGSTONE DE, JONES GC, SMITH Y, ANDREW R, KENYON CJ, WALKER BR: Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats. Endocrinology (2000) 141:560-563.
70. PAULMYER-LACROIX O, BOULLU S, OLIVER C, ALESSI MC, GRIND M: Expression of the mRNA coding for 11β-hydroxysteroid dehydrogenase Type 1 in adipose tissue from obese patients: an in situ hybridization study. J. Clin. Endocrinol. Metab. (2002) 87:2701-2705.
71. LINDSAY RS, WAKE DJ, NAIR S et al.: Subcutaneous adipose 11β-hydroxysteroid dehydrogenase Type 1 activity and mRNA levels arc associated with adiposity and insulinaemia in Pima Indians and Caucasians. J. Clin. Endocrinol. Metab. (2003) 88:2738-2744.
72. WAKE DJ, RASK E, LIVINGSTONE DE, SODERBERG S, OLSSON T, WALKER BR: Local and systemic impact of transcriptional upregulation of 11β-hydroxysteroid dehydrogenase Type 1 in adipose tissue in human obesity. J. Clin. Endocinol Metab. (2003) 88:2983-2988.
73. TOMLINSON JW, SINHA B, BUJALSKA I, HEWISON M, STEWART PM: Expression of 11β-hydroxysteroid dehydrogenase Type 1 in adipose tissue is not increased in human obesity. J. Clin. Endocrinol. Metab. (2002) 87:5630-5635.
74. PHILLIPOU G, PALERMO M, SHACKLETON CH: Apparent cortisone reductase deficiency: a unique form of hypercortisolism. J. Clin. Endocrinol. Metab. (1996) 81:3855-3860.
75. JAMIESON A, WALLACE AM, WALKER BR et al.: Apparent cortisone reductase deficiency: a functional defect in 11β-hydroxysteroid dehydrogenase Type 1. J. Clin. Endocrinol. Metab. (1999) 84:3570-3574.
76. TOMLINSON JW, MOORE J, COOPER MS et al.: Regulation of expression of 11β-hydroxysteroid dehydrogenase Type 1 in adipose tissue: tissue-specific induction by cytokines. Endocrinology (2001) 142:1982-1989.
77. LIU Y, NAKAGAWA Y, WANG Y et al.: Leptin activation of corticosterone production in hepatocytes may contribute to the reversal of obesity and hyperglycemia in leptin-deficient ob/ob mice. Diabetes (2003) 52:1409-1416.
78. ANDREWS RC, HERLIHY O, LIVINGSTONE DE, ANDREW R, WALKER BR: Abnormal corrisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance. J. Clin. Endocrinol Metab. (2002) 87:5587-5593.
79. DRAPER N, ECHWALD SM, LAVERY GG et al.: Association studies between microsatellite markers within the gene encoding human 11β-hydroxysteroid dehydrogenase Type 1 and body mass index, waist to hip ratio, and glucocordcoid metabolism. J. Clin. Endocninol. Metab. (2002) 87:4984-4990.
80. STEWART PM, VALENTINO R, WALLACE AM, BURT D, SHACKLETON CH, EDWARDS CR: Mineralocorticoid activity of liquorice: 11β-hydroxysteroid dehydrogenase deficiency comes of age. Lancet (1987) 2:821-824.
81. TEELUCKSINGH S, BENEDIKTSSON R, LINDSAY RS et al.: Liquorice. Lancet (1991) 337:1549.
82. LATIF SA, CONCA TJ, MORRIS DJ: The effects of the liquorice derivative, glycyrrhetinic acid, on hepatic 3α- and 3β-hydroxysteroid dehydrogenases and 5α- and 5β-reductase pathways of metabolism of aldosterone in male rats. Steroids (1990) 55:52-58.
83. ULLIAN ME, HAZEN-MARTIN DJ, WALSH LG, DAVDA RK, EGAN BM: Carbenoxolone damages endothelium and enhances vasoconstrictor action in aortic rings. Hypertension (1996) 27:1346-1352.
84. + currents underlying the action of endothelium-derived hyperpolarizing factor in guinea-pig, rat and human blood vessels. J. Physiol. (Lond.) (2001) 531:359-373.
85. TARE M, COLEMAN HA, PARKINGTON HC: Glycyrrhetinic derivatives inhibit hyperpolarization in endothelial cells o guinea pig and rat arteries. Am. J. Physiol. Heart Circ. Physiol. (2002) 282:H335-H341.
86. KENNY LC, BAKER PN, KENDALL DA, RANDALL MD, DUNN WR: The role of gap junctions in mediating endothelium-dependent responses to bradykinin in myometrial small arteries isolated from pregnant women. Br. J. Pharmacol. (2002) 136:1085-1088.
87. GOTO K, FUJII K, KANSUI Y, ABE I, IIDA M: Critical role of gap junctions in endothelium-dependent hyperpolarization in rat mesenteric arteries. Clin. Exp. Pharmacol. Physiol. (2002) 29:595-602.
88. CHAYTOR AT, MARSH WL, HUTCHESON IR, GRIFFITH TM: Comparison of glycyrrhetinic acid isoforms and carbenoxolone as inhibitors of EDHF-type relaxations mediated via gap junctions. Endothelium (2000) 7:265-278.
89. WALKER BR, CONNACHER AA, LINDSAY RM, WEBB DJ, EDWARDS CR: Carbenoxolone increases hepatic insulin sensitivity in man: a novel role for 11-oxosteroid reductase in enhancing glucocorticoid receptor activation. J. Clin. Endocrinol. Metab. (1995) 80:3155-3159.
90. ANDREWS RC, ROOYACKERS O, WALKER BR: Effects of the 11β-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with Type 2 diabetes. J. Clin. Endocrinol. Metab. (2003) 99:285-291.
91. LIVINGSTONE DE, WALKER BR: Is 11β-hydroxysteroid dehydrogenase Type 1 a therapeutic target? Effects of carbenoxolone in lean and obese Zucker rats. J. Pharmacol. Exp. Ther. (2003) 305:167-172.
92. JELLINCK PH, MONDER C, MCEWEN BS, SAKAI RR: Differential inhibition of 11β-hydroxysteroid dehydrogenase by carbenoxolone in rat brain regions and peripheral tissues. J. Steroid Biocbem. Mol. Biol. (1993) 46:209-213.
93. SANDEEP TC, MACLULLICH AM, YAU JL et al.: 11β-Hydroxysteroid dehydrogenase Type 1 is expressed in human brain: inhibition with carbenoxolone improves cognitive function in healthy elderly men. Endocr. Abstr. (2002) 3:OC41. Abstract.
94. BARF T, VALLGARDA J, EMOND R et al.: Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs. Discovery of potent and selective inhibitors of the 11β-hydroxysteroid dehydrogenase Type 1. J. Med. Chem. (2002) 45:3813-3815.
95. ALBERTS P, ENGBLOM L, EDLING N et al.: Selective inhibition of 11β-hydroxysteroid dehydrogenase Type 1 decreases blood glucose concentrations in hyperglycaemic mice. Diabetologia (2002) 45:1528-1532.
96. HUNDERTMARK S, DILL A, EBERT A et al.: Foetal lung maturation in 11β-hydroxysteroid dehydrogenase Type 1 knockout mice. Horm. Metab. Res. (2002) 34:545-549.
97. HUNDERTMARK S, DILL A, BUHLER H et al.: 11β-hydroxysteroid dehydrogenase Type 1: a new regulator of fetal lung maturation. Horm. Metab. Res. (2002) 34:537-544.
98. HADOKE PW, CHRISTY C, KOTELEVTSEV YV et al.: Endothelial cell dysfunction in mice after transgenic knockout of Type 2, but not Type 1, 11β-hydroxysteroid dehydrogenase. Circulation (2001) 104:2832-2837.
99. COOPER MS, BUJALSKA I, RABBITT E, WALKER EA, BLAND R, SHEPPARD MC: Modulation of 11 [β]-hydroxysteroid dehydrogenase isozymes by proinflammatory cytokines in osteoblasts: an autocrine switch from glucocorticoid inactivation to activation. J. Bone Miner. Res. (2001) 16:1037-1044.
100. COOPER MS, RABBITT EH, GODDARD PE, BARTLETT WA, HEWISON M, STEWART PM: Osteoblastic 11β-hydroxysteroid dehydrogenase Type 1 activity increases with age and glucocorticoid exposure. J. Bone Miner. Res. (2002) 17:979-986.
101. THIERINGER R. LE GRAND CB, CARBIN L, CAI TQ, WONG B, WRIGHT SD: 11[β]-Hydroxysteroid dehydrogenase Type 1 is induced in human monocytes upon differentiation to macrophages. J. Immunol. (2001) 167:30-35.
102. EVAGELATOU M, PETERSON SL, COOKE BA: Leukocytes modulate 11β-hydroxysteroid dehydrogenase (11β-HSD) activity in human granulosa - lutein cell cultures. Mol. Cell. Endocrinol. (1997) 133:81-88.
103. TETSUKA M, HAINES LC, MILNE M, SIMPSON GE, HILLIER SG: Regulation of 11β-hydroxysteroid dehydrogenase Type 1 gene expression by LH and interleukin-1β in cultured rat granulosa cells. J. Endocrinol. (1999) 163:417-423.
104. CAI TQ WONG B, MUNDT SS, THIERINGER R, WRIGHT SD: Induction of 11 [β]-hydroxysteroid dehydrogenase Type 1 but not -2 in human aortic smooth muscle cells by inflammatory stimuli. J. Steroid Biochem. Mol. Biol. (2001) 77:117-122.
105. SOUNESS GW, LATIF SA. LAURENZO JL, MORRIS DJ: 11α- and 11β-hydroxyprogesterone, potent inhibitors of 11β-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat. Endocrinology (1995) 136:1809-1812.
106. BREM AS, BINA RB, KING T, MORRIS DJ: 11βOH-progesterone affects vascular glucocorticoid metabolism and contractile response. Hypertension (1997) 30:449-454.
107. MORITA H, ZHOU M, FOECKING MF et al.: 11β-Hydroxysteroid dehydrogenase Type 2 complementary deoxyribonucleic acid stably transfected into Chinese hamster ovary cells: specific inhibition by 11α-hydroxyprogesterone. Endocrinology (1996) 137:2308-2314.
108. SHIMOYAMA Y, HIRABAYASHI K, MATSUMOTO H, SATO T, SHIBATA S, INOUE H: Effects of glycyrrhetinic acid derivatives on hepatic and renal 11β-hydroxysteroid dehydrogenase activities in rats. J. Pharm. Pharmacol. (2003) 55-811-817.
109. KATO H, KANAOKA M, YANO S, KOBAYASHI M: 3-Monoglucuronyl-glycyrrhetinic add is a major metabolite that causes licorice-induced pseudoaldosteronism. J. Clin. Endocrinol. Metab. (1995) 80:1929-1933.
110. MORRIS DJ, SEMAFUKO WE, LATIF SA, VOGEL B, GRIMES C, SHEFF MF: Detection of glycyrrhetinic acid-like factors (GALFs) in human urine. hypertension (1992) 20:356-360.
111. + retention. Steroids (1994) 59:352-356.
112. SEMAFUKO WE, SHEFF MF, GRIMES CA et al.: Inhibitors of 11β-hydroxysteroid dehydrogenase and 5β-steroid reductase in urine from patients with congestive heart failure. Ann. Clin. Lab. Sci. (1993) 23:456-461.
113. WALKER BR, AGGARWAL I, STEWART PM, PADFIELD PL, EDWARDS CR: Endogenous inhibitors of 11β-hydroxysteroid dehydrogenase in hypertension. J. Clin. Endocrinol. Metab. (1995) 80:529-533.
114. WALKER BR, WILLIAMSON PM, BROWN MA, HONOUR JW, EDWARDS CR, WHITWORTH JA: 11β-Hydroxysteroid dehydrogenase and its inhibitors in hypertensive pregnancy. Hypertension (1995) 25:626-630.
115. TAKEDA Y, MIYAMORI I, IKI K et al.: Endogenous renal 11β-hydroxysteroid dehydrogenase inhibitory factors in patients with low-renin essential hypertension. Hypertension (1996) 27:197-201.
116. ROSEBOOM TJ, VAN DER MEULEN JP, RAVELLI AJ et al.: Blood pressure in adults after prenatal exposure to famine. J. Hypertens. (1999) 17:325-330.
117. LATIF SA, SHEFF MF, RIBEIRO CE, MORRIS DJ: Selective inhibition of sheep kidney 11β-hydroxysteroid dehydrogenase isoform 2 activity by 5α-roduced (but not 5β) derivatives of adrenocorticosteroids. Steroids (1997) 62:230-237.
118. THURSTON LM, JONAS KC, ABAYASEKARA DR, MICHAEL AE: Ovarian modulaxors of 11βA-hydroxysteroid dehydrogenase (11βHSD) activity in follicular fluid from bovine and porcine large antral follicles and spontaneous ovarian cysts. Biol. Reprod. (2003) 68:2157-2163.
119. BUHLER H, PERSCHEL FH, HIERHOLZER K: Inhibition of rat renal 11β-hydroxysteroid dehydrogenase by steroidal compounds and triterpenoids; structure/function relationship. Biochim. Biophys. Acta (1991)1075:206-212.
120. STAUFFER AT, ROCHAT MY, DICK B, FREY FJ, ODERMATT A: Chenodeoxycholic acid and deoxycholic acid inhibit 11β-hydroxysteroid dehydrogenase Type 2 and cause cortisol-induced transcriptional activation of the mineralocorticoid receptor. J. Biol. Chem. (2002) 277:26286-26292.
121. PERSCHEL FH, BUHLER H, HIERHOLZER K: Bile acids and their amidates inhibit 11β-hydroysteroid dehydrogenase obtained from rat kidney. Pflugers Arch. (1991) 418:538-543.
122. ESCHER G, NAWROCKI A. STAUB T et al.: Down-regulation of hepatic and renal 11β-hydroxysteroid dehydrogenase in rats with liver cirrhosis. Gastroeterology (1998) 114:175-184.
123. HOMMA M, OKA K, NIITSUMA T, ITOH H: A novel 11β-hydroxysteroid dehydrogenase inhibitor contained in Saiboku-To, a herbal remedy for steroid-dependent bronchial asthma. J. Pharm. Pharmacol. (1994) 46:305-309.
124. HOMMA M, OKA K, IKESHIMA K et al.: Different effects of traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics. J. Pharm. Pharmacol. (1995) 47:687-692.
125. SONG D, LORENZO B, REIDENBERG MM: Inhibition of 11β-hydroxysteroid dehydrogenase by gossypol and bioflavonoids. J. Lab. Clin. Med. (1992) 120:792-797.
126. WANG MS, LORENZO JB, REIDENBERG MM: NAD- and NADP-dependent 11β-hydroxysteroid dehydrogenase isoforms in guinea pig kidney with gossypol inhibition. Acta Pharm. Sin. (1997) 18:481-485.
127. RAVEN PW, CHECKLEY SA, TAYLOR NF: Extra-adrenal effects of metyrapone include inhibition of the 11-oxoreductase activity of 11β-hydroxysteroid dehydrogenase: a model for 11-HSD I deficiency. Clin. Endocrinol. (Oxf.) (1995) 43:637-644.
128. THOMSON LM, RAVEN PW, SMITH KE, HINSON JP: Effects of metyrapone on hepatic cortisone - cortisol conversion in the rat. Endocr. Res. (1998) 24:607-611.
129. SAMPATH-KUMAR R. YU M, KHALIL MW, YANG K: Metyrapone is a competitive inhibitor of 11β-hydroxysteroid dehydrogenase Type 1 reductase. J. Steroid Biochem. Mol. Biol. (1997) 62:195-199.
130. FUSTER D, ESCHER G, VOGT B et al.: Furosemide inhibits 11β-hydroxysteroid dehydrogenase Type 2. Endocrinology (1998) 139:3849-3854.
131. ESCHER G, MEYER KV, VISHWANATH BS, FREY BM, FREY FJ: Furosemide inhibits 11β-hydroxysteroid dehydrogenase in vitro and in vivo. Endocrinology (1995) 136:1759-1765.
132. LEE YS, LORENZO BJ, KOUFIS T, REIDENBERG MM: Grapefruit juice and its flavonoids inhibit 11β-hydroxysteroid dehydrogenase. Clin. Pharmacol. Ther. (1996) 59:62-71.
133. ZHANG YD, LORENZO B, REIDENBERG MM: Inhibition of 11β-hydrosteroid dehydrogenase obtained from guinea pig kidney by fuosemide, naringenin and some other compound. J. Steroid Biochem. Mol. Biol. (1994) 49:81-85.
134. PALERMO M, ARMANINI D, SHACKLETON CH et al.: Furosemide and 11β-hydroxysteroid dehydrogenase activity, in man. Exp. Clin. Endocrinol. Diabetes (2002) 110:272-276.
135. ZHANG YD, WANG MS: Inhibition of 11β-hydroxysteroid dehydrogenase obtained from guinea pig kidney by some bioflavonoids and triterpenoids. Acta Pharm. Sin. (1997) 18:240-244.
136. PALERMO M, ARMANINI D, DELITALA G: Grapefruit juice inhibits 11β-hydroxysteroid dehydrogenase in vivo, in man. Clin. Endocrinol. (Oxf.) (2003) 59:143-144.