11β-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess

Endocrine Reviews

Volumn 18, Issue 1, 1997, Pages 135-156

  White, Perrin C ^a,b   Mune, Tomoatsu ^a,c   Agarwal, Anil K ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c GIFU UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE; ALDOSTERONE; CORTICOTROPIN; CORTISONE; ENZYME INHIBITOR; HYDROCORTISONE; ISOENZYME; MINERALOCORTICOID RECEPTOR; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE;

ARTICLE; CORTICOSTEROID METABOLISM; ECTOPIC CORTICOTROPIN PRODUCTION; ENZYME DEFICIENCY; ESSENTIAL HYPERTENSION; GENE EXPRESSION; GENE LOCUS; GENE MUTATION; GLYCYRRHIZA; HORMONE RECEPTOR INTERACTION; HUMAN; INTOXICATION; KIDNEY; NONHUMAN; PLACENTA; PRIORITY JOURNAL; TISSUE DISTRIBUTION;

11-BETA-HYDROXYSTEROID DEHYDROGENASES; ACTH SYNDROME, ECTOPIC; ALDOSTERONE; GLYCYRRHIZA; HUMANS; HYDROXYSTEROID DEHYDROGENASES; HYPERTENSION; ISOENZYMES; MINERALOCORTICOIDS; MUTATION; PLANTS, MEDICINAL; RECEPTORS, MINERALOCORTICOID; SYNDROME;

EID: 0031046241     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.18.1.135     Document Type: Article

References (210)

1. Wilson JD, Griffin JE, Russell DW 1993 Steroid 5 alpha-reductase 2 deficiency. Endocr Rev 14:577-593
2. Hench PS, Slocumb CH, Polley HF, Kendall EC 1950 Effect of cortisone and pituitary adrenocorticotropic hormone (ACTH) on rheumatic diseases. J Am Med Assoc 144:1327-1335
3. Boland EW, Headley NE 1996 Oral use of cortisone acetate. J Am Med Assoc 145:8-11
4. Hollander JL, Brown EM, Jessar RA, Brown CY 1951 Hydrocortisone and cortisone injected into arthritic joints. Comparative effects of and use of hydrocortisone as a local antiarthritic agent. J Am Med Assoc 147:1629-1635
5. Mason HL 1950 Isolation of adrenal cortical hormones from urine: 17-hydroxycorticosterone and 17-hydroxy-11-dehydrocorticosterone. J Biol Chem 182:131-149
6. Amelung D, Huebener HJ, Roka L, Meyerheim G 1953 Conversion of cortisone to compound F. J Clin Endocrinol Metab 13:1125
7. Hubener HJ, Fukushima DK, Gallagher TF 1956 Substrate specificity of enzymes reducing the 11- and 20-keto groups of steroids. J Biol Chem 220:499-511
8. Brien TG 1981 Human corticosteroid binding globulin. Clin Endocrinol (Oxf) 14:193
9. White PC, Pescovitz OH, Cutler Jr GB 1995 Synthesis and metabolism of corticosteroids. In: Becker KL (ed) Principles and Practice of Endocrinology and Metabolism. Lippincott, Philadelphia, pp 647-662
10. Bongiovanni AM, Cohn RM 1970 Clinical aspects of steroid conjugation. In: Bernstein S, Solomon S (eds) Chemical and Biological Aspects of Steroid Conjugation. Springer-Verlag, New York, pp 410-450
11. Duchatelle P, Ohara A, Ling BN, Kemendy AE, Kokko KE, Matsumoto PS, Eaton DC 1992 Regulation of renal epithellial sodium channels. Mol Cell Biochem 114:27-34
12. Palmer LG, Frindt G 1992 Regulation of apical membrane Na and K channels in rat renal collecting tubules by aldosterone. Semin Nephrol 12:37-43
13. Horisberger JD, Rossier BC 1992 Aldosterone regulation of gene transcription leading to control of ion transport. Hypertension 19: 221-227
14. Wehling M 1995 Nongenomic aldosterone effects: the cell membrane as a specific target of mineralocorticoid action. Steroids 60: 153-156
15. Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM 1987 Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237:268-275
16. Pearce D, Yamamoto KR 1993 Mineralocorticoid and glucocorticoid receptor activities distinguished by nonreceptor factors at a composite response element. Science 259:1161-1165
17. Robertson NM, Schulman G, Karnik S, Alnemri E, Litwack G 1993 Demonstration of nuclear translocation of the mineralocorticoid receptor (MR) using an anti-MR antibody and confocal laser scanning microscopy. Mol Endocrinol 7:1226-1239
18. Krozowski ZS, Funder JW 1983 Renal mineralocorticoid receptors and hippocampal corticosterone binding species have identical intrinsic steroid specificity. Proc Natl Acad Sci USA 80:6056-6060
19. Beaumont K, Fanestil DD 1983 Characterization of rat brain aldosterone receptors reveals high affinity for corticosterone. Endocrinology 113:2043-2051
20. Stephenson G, Krozowski ZS, Funder JW 1984 Extravascular CBG-like sites in rat kidney and mineralocorticoid receptor specificity. Am J Physiol 246:F227-F233
21. Sheppard K, Funder JW 1987 Mineralocorticoid specificity of renal type I receptors: in vivo binding studies. Am J Physiol 252:E224-E229
22. Lombes M, Kenouch S, Souque A, Farman N, Rafestin-Oblin ME 1994 The mineralocorticoid receptor discriminates aldosterone from glucocorticoids independently of the 11 beta-hydroxysteroid dehydrogenase. Endocrinology 135:834-840
23. Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CH, Edwards CR 1987 Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. Lancet 2:821-824
24. Edwards CR, Stewart PM, Burt D, Brett L, McIntyre MA, Sutanto WS, de Kloet ER, Monder C 1988 Localisation of 11 beta-hydroxysteroid dehydrogenase-tissue specific protector of the mineralocorticoid receptor. Lancet 2:986-989
25. Funder JW, Pearce PT, Smith R, Smith AI 1988 Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242:583-585
26. Werder EA, Zachmann M, Vollmin JA, Veyrat R, Prader A 1974 Unusual steroid excretion in a child with low-renin hypertension. Res Steroids 6:385-389
27. New MI, Levine LS, Biglieri EG, Pareira J, Ulick S 1977 Evidence for an unidentified steroid in a child with apparent mineralocorticoid hypertension. J Clin Endocrinol Metab 44:924-933
28. Ulick S, Ramirez LC, New MI 1977 An abnormality in steroid reductive metabolism in a hypertensive syndrome. J Clin Endocrinol Metab 44:799-802
29. Ulick S, Levine LS, Gunczler P, Zanconato C, Ramirez LC, Rauh W, Rosler A, Bradlow HL, New MI 1979 A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol. J Clin Endocrinol Metab 49:757-764
30. Liddle GW, Bledsoe T, Coppage WS 1963 A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans Assoc Am Physicians 76:199-213
31. Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, Gill Jr JR, Ulick S, Milora RV, Findling JW, Canessa CM, Rossier BC, Lifton RP 1994 Liddle's syndrome: heritable human hypertension caused by mutations in the β subunit of the epithelial sodium channel. Cell 79:407-414
32. Hansson JH, Nelson-Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, Canessa C, Iwasaki T, Rossier B, Lifton RP 1995 Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet 11: 76-82
33. Winter JS, McKenzie JK 1977 A syndrome of low-renin hypertension in children. In: New MI, Levine LS (eds) Juvenile Hypertension. Raven Press, New York, pp 123-131
34. Shackleton CH, Rodriguez J, Arteaga E, Lopez JM, Winter JS 1985 Congenital 11 beta-hydroxysteroid dehydrogenase deficiency associated with juvenile hypertension: corticosteroid metabolite profiles of four patients and their families. Clin Endocrinol (Oxf) 22: 701-712
35. Igarashi Y, Egi S, Takehiro A, Ohzeki T, Kawaguchi H 1979 Studies on the metabolic abnormality of cortisol and corticosterone in a case of dexamethasone responsive mineralocorticoid excess. Folia Endocrinol Jpn 55:1341-1357
36. Shackleton CH, Honour JW, Dillon MJ, Chantler C, Jones RW 1980 Hypertension in a four-year-old child:gas chromatographic and mass spectrometric evidence for deficient hepatic metabolism of steroids. J Clin Endocrinol Metab 50:786-792
37. Fiselier TJ, Otten BJ, Monnens LA, Honour J, van Munster PJ 1982 Low-renin, low-aldosterone hypertension and abnormal cortisol metabolism in a 19-month-old child. Horm Res 16:107-114
38. Honour JW, Dillon MJ, Levin M, Shah V 1983 Fatal, low renin hypertension associated with a disturbance of cortisol metabolism. Arch Dis Child 58:1018-1020
39. Harinck HI, van Brummelen P, van Seters AP, Moolenaar AJ 1984 Apparent mineralocorticoid excess and deficient 11 beta-oxidation of cortisol in a young female. Clin Endocrinol (Oxf) 21:505-514
40. Monder C, Shackleton CH, Bradlow HL, New MI, Stoner E, Iohan F, Lakshmi V 1986 The syndrome of apparent mineralocorticoid excess: its association with 11 beta-dehydrogenase and 5 beta-reductase deficiency and some consequences for corticosteroid metabolism. J Clin Endocrinol Metab 63:550-557
41. Dimartino-Nardi J, Stoner E, Martin K, Balfe JW, Jose PA, New MI 1987 New findings in apparent mineralocorticoid excess. Clin Endocrinol (Oxf) 27:49-62
42. Batista MC, Mendonca BB, Kater CE, Arnhold IJ, Rocha A, Nicolau W, Bloise W 1986 Spironolactone-reversible rickets associated with 11 beta-hydroxysteroid dehydrogenase deficiency syndrome. J Pediatr 109:989-993
43. Stewart PM, Corrie JE, Shackleton CH, Edwards CR 1988 Syndrome of apparent mineralocorticoid excess. A defect in the cortisol-cortisone shuttle. J Clin Invest 82:340-349
44. Milford DV, Shackleton CH, Stewart PM 1995 Mineralocorticoid hypertension and congenital deficiency of 11 beta-hydroxysteroid dehydrogenase in a family with the syndrome of 'apparent' mineralocorticoid excess. Clin Endocrinol (Oxf) 43:241-246
45. Wilson RC, Krozowski ZS, Li K, Obeyesekere VR, Razzaghy-Azar M, Harbison MD, Wei JQ, Shackleton CH, Funder JW, New MI 1995 A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab 80:2263-2266
46. Mune T, Rogerson FM, Nikkila H, Agarwal AK, White PC 1995 Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase. Nat Genet 10:394-399
47. Wilson RC, Harbison MD, Krozowski ZS, Funder JW, Shackleton CH, Hanauske-Abel HM, Wei JQ, Hertecant J, Moran A, Neiberger RE, Balfe JW, Fattah A, Daneman D, Licholai T, New MI 1995 Several homozygous mutations in the gene for 11β-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab 80:3145-3150
48. Kitanaka S, Tanae A, Hibi I 1996 Apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase deficiency: a possible cause of intrauterine growth retardation. Clin Endocrinol (Oxf) 44:353-359
49. Bournot P, Pitoizet N, Zachmann M, Maume BF 1982 Partial characterization of unusual polar steroids in the urine of a child with low renin hypertension. J Steroid Biochem 16:467-477
50. Oberfield SE, Levine LS, Carey RM, Greig F, Ulick S, New MI 1983 Metabolic and blood pressure responses to hydrocortisone in the syndrome of apparent mineralocorticoid excess. J Clin Endocrinol Metab 56:332-339
51. Riddle MC, McDaniel PA 1994 Renal 11 beta-hydroxysteroid dehydrogenase activity is enhanced by ramipril and captopril. J Clin Endocrinol Metab 78:830-834
52. Davis EA, Morris DJ 1991 Medicinal uses of licorice through the millennia: the good and plenty of it. Mol Cell Endocrinol 78:1-6
53. Card WI, Mitchell W, Strong JA, Taylor NR, Tompsett SL, Wilson JMG 1953 Effects of liquorice and its derivatives on salt and water metabolism. Lancet 1:663-668
54. Conn JW, Rovner DR, Cohen EL 1968 Licorice-induced pseudoaldosteronism, hypertension, hypokalemia, aldosteronopenia, and suppressed plasma renin activity. J Am Med Assoc 205:492-496
55. Epstein MT, Espiner EA, Donald RA, Hughes H 1977 Liquorice toxicity and the renin-angiotensin-aldosterone axis in man. Br Med J 1:209-210
56. Farese Jr RV, Biglieri EG, Shackleton CH, Irony I, Gomez-Fontes R 1991 Licorice-induced hypermineralocorticoidism. N Engl J Med 325:1223-1227
57. Borst JG, de Vries LA, ten Holt SP, Molhuysen JA 1953 Synergistic action of liquorice and cortisone in Addison's and Simmond's disease. Lancet 1:657-663
58. Souness GW, Morris DJ 1991 The "mineralocorticoid-like" actions conferred on corticosterone by carbenoxolone are inhibited by the mineralocorticoid receptor (type I) antagonist RU28318. Endocrinology 129:2451-2456
59. Mac Kenzie MA, Hoefnagels WH, Jansen RW, Benraad TJ, Kloppenborg PW 1990 The influence of glycyrrhetinic acid on plasma cortisol and cortisone in healthy young volunteers. J Clin Endocrinol Metab 70:1637-1643
60. Monder C, Stewart PM, Lakshmi V, Valentino R, Burt D, Edwards CR 1989 Licorice inhibits corticosteroid 11 beta-dehydrogenase of rat kidney and liver: m vivo and in vitra studies. Endocrinology 125:1046-1053
61. Hierholzer K, Siebe H, Fromm M 1990 Inhibition of 11 beta-hydroxysteroid dehydrogenase and its effect on epithelial sodium transport. Kidney Int 38:673-678
62. Latif SA, Conca TJ, Morris DJ 1990 The effects of the licorice derivative, glycyrrhetinic acid, on hepatic 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha- and 5 beta-reductase pathways of metabolism of aldosterone in male rats. Steroids 55: 52-58
63. Morris DJ, Souness GW 1990 The 11 beta-OHSD inhibitor, carbenoxolone, enhances Na retention by aldosterone and 11-deoxycorticosterone. Am J Physiol 258:F756-F759
64. Stewart PM, Wallace AM, Atherden SM, Shearing CH, Edwards CR 1990 Mineralocorticoid activity of carbenoxolone: contrasting effects of carbenoxolone and liquorice on 11 beta-hydroxysteroid dehydrogenase activity in man. Clin Sci 78:49-54
65. Escher G, Meyer KV, Vishwanath BS, Frey BM, Frey FJ 1995 Furosemide inhibits 11 beta-hydroxysteroid dehydrogenase in vitro and in vivo. Endocrinology 136:1759-1765
66. Zhang YD, Lorenzo B, Reidenberg MM 1994 Inhibition of 11 beta-hydroxysteroid dehydrogenase obtained from guinea pig kidney by furosemide, naringenin and some other compounds. J Steroid Biochem Mol Biol 49:81-85
67. Song D, Lorenzo B, Reidenberg MM 1992 Inhibition of 11 beta-hydroxysteroid dehydrogenase by gossypol and bioflavonoids. J Lab Clin Med 120:792-797
68. Lee YS, Lorenzo BJ, Koufis T, Reidenberg MM 1996 Grapefruit juice and its flavonoids inhibit 11 β-hydroxysteroid dehydrogenase. Clin Pharmacol Ther 59:62-71
69. Walker BR, Campbell JC, Fraser R, Stewart PM, Edwards CR 1992 Mineralocorticoid excess and inhibition of 11 beta-hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome. Clin Endocrinol (Oxf) 37:483-492
70. Ulick S, Wang JZ, Blumenfeld JD, Pickering TG 1992 Cortisol inactivation overload: a mechanism of mineralocorticoid hypertension in the ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 74:963-967
71. Diederich S, Quinkler M, Miller K, Heilmann P, Schoneshofer M, Oelkers W 1996 Human kidney 11 beta-hydroxysteroid dehydrogenase: regulation by adrenocorticotropin? Eur J Endocrinol 134: 301-307
72. Reinisch J, Simon NG, Karwo WG 1978 Prenatal exposure to prednisone in humans and animals retards intrauterine growth. Science 202:436-438
73. Edwards CR, Benediktsson R, Lindsay RS, Seckl JR 1993 Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension? Lancet 341:355-357
74. Benediktsson R, Lindsay RS, Noble J, Seckl JR, Edwards CR 1993 Glucocorticoid exposure in utero: new model for adult hypertension. Lancet 341:339-341
75. Law CM, Barker DJ, Bull AR, Osmond C 1991 Maternal and fetal influences on blood pressure. Arch Dis Child 66:1291-1295
76. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME 1989 Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. Br Med J 298:564-567
77. Barker DJ, Bull AR, Osmond C, Simmonds SJ 1990 Fetal and placental size and risk of hypertension in adult life. Br Med J 301:259-262
78. Law CM, de Swiet M, Osmond C, Fayers PM, Barker DJ, Cruddas AM, Fall CH 1993 Initiation of hypertension m utero and its amplification throughout life. Br Med J 306:24-27
79. Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS 1993 Fetal nutrition and cardiovascular disease in adult life. Lancet 341:938-941
80. Levine RS, Hennekens CH, Jesse MJ 1994 Blood pressure in prospective population based cohort of newborn and infant twins. Br Med J 308:298-302
81. Stewart PM, Rogerson FM, Mason JI 1995 Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis. J Clin Endocrinol Metab 80:885-890
82. Morris DJ, Semafuko WE, Latif SA, Vogel B, Grimes CA, Sheff MF 1992 Detection of glycyrrhetinic acid-like factors (GALFs) in human urine. Hypertension 20:356-360
83. Walker BR, Aggarwal I, Stewart PM, Padfield PL, Edwards CR 1995 Endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase in hypertension. J Clin Endocrinol Metab 80:529-533
84. Takeda Y, Miyamori I, Iki K, Inaba S, Furukawa K, Hatakeyama H, Yoneda T, Takeda R 1996 Endogenous renal 11β-hydroxysteroid dehydrogenase inhibitory factors in patients with low-renin essential hypertension. Hypertension 27:197-201
85. Souness GW, Latif SA, Laurenzo JL, Morris DJ 1995 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat. Endocrinology 136:1809-1812
86. Soro A, Ingram MC, Tonolo G, Glorioso N, Fraser R 1995 Evidence of coexisting changes in 11 beta-hydroxysteroid dehydrogenase and 5 beta-reductase activity in subjects with untreated essential hypertension. Hypertension 25:67-70
87. Walker BR, Stewart PM, Shackleton CH, Padfield PL, Edwards CR 1993 Deficient inactivation of cortisol by 11 beta-hydroxysteroid dehydrogenase in essential hypertension. Clin Endocrinol (Oxf) 39:221-227
88. Iki K, Miyamori I, Hatakeyama H, Yoneda T, Takeda Y, Takeda R, Dai QL 1994 The activities of 5 beta-reductase and 11 beta-hydroxysteroid dehydrogenase in essential hypertension. Steroids 59:656-660
89. Santini DL, Lorenzo BJ, Koufis T, Reidenberg MM 1995 Cortisol metabolism in hypertensive patients who do and do not develop hypokalemia from diuretics. Am J Hypertens 8:516-519
90. Walker BR, Best R, Shackleton CH, Padfield PL, Edwards CR 1996 Increased vasoconstrictor sensitivity to glucocorticoids in essential hypertension. Hypertension 27:190-196
91. Phillipou G, Higgins BA 1985 A new defect in the peripheral conversion of cortisone to Cortisol. J Steroid Biochem 22:435-436
92. Nikkila H, Tannin GM, New MI, Taylor NF, Kalaitzoglou G, Monder C, White PC 1993 Defects in the HSD11 gene encoding 11β-hydroxysteroid dehydrogenase are not found in patients with apparent mineralocorticoid excess or 11-oxoreductase deficiency. J Clin Endocrinol Metab 77:687-691
93. 92a. Phillipov G, Palermo M, Shackleton CH 1996 Apparent cortisone reductase deficiency: a unique form of hypercortisolism. J Clin Endocrinol Metab 81:3855-3860
94. Sann L, Revol A, Zachmann M, Legrand JC, Bethenod M 1976 Unusual low plasma renin hypertension in a child. J Clin Endocrinol Metab 43:265-271
95. Ulick S, Tedde R, Mantero F 1990 Pathogenesis of the type 2 variant of the syndrome of apparent mineralocorticoid excess. J Clin Endocrinol Metab 70:200-206
96. Ulick S, Chan CK, Rao KN, Edassery J, Mantero F 1989 A new form of the syndrome of apparent mineralocorticoid excess. J Steroid Biochem 32:209-212
97. Mantero F, Tedde R, Opocher G, Dessi Fulgheri P, Arnaldi G, Ulick S 1994 Apparent mineralocorticoid excess type II. Steroids 59:80-83
98. Ulick S, Tedde R, Wang JZ 1992 Defective ring A reduction of cortisol as the major metabolic error in the syndrome of apparent mineralocorticoid excess. J Clin Endocrinol Metab 74:593-599
99. Monder C, White PC 1993 11 Beta-hydroxysteroid dehydrogenase. Vitam Horm 47:187-271
100. Walker BR, Connacher AA, Lindsay RM, Webb DJ, Edwards CR 1995 Carbenoxolone increases hepatic insulin sensitivity in man: a novel role for 11-oxosteroid reductase in enhancing glucocorticoid receptor activation. J Clin Endocrinol Metab 80:3155-3159
101. Lakshmi V, Monder C 1988 Purification and characterization of the corticosteroid 11 beta-dehydrogenase component of the rat liver 11 beta-hydroxysteroid dehydrogenase complex. Endocrinology 123: 2390-2398
102. Whitworth JA, Stewart PM, Burt D, Atherden SM, Edwards CR 1989 The kidney is the major site of cortisone production in man. Clin Endocrinol (Oxf) 31:355-361
103. Bonvalet JP, Doignon I, Blot-Chabaud M, Pradelles P, Farman N 1990 Distribution of 11 beta-hydroxysteroid dehydrogenase along the rabbit nephron. J Clin Invest 86:832-837
104. Naray-Fejes-Toth A, Watlington CO, Fejes-Toth G 1991 11 beta-Hydroxysteroid dehydrogenase activity in the renal target cells of aldosterone. Endocrinology 129:17-21
105. Kenouch S, Alfaidy N, Bonvalet JP, Farman N 1994 Expression of 11 beta-OHSD along the nephron of mammals and humans. Steroids 59:100-104
106. Rusvai E, Naray-Fejes-Toth A 1993 A new isoform of 11 beta-hydroxysteroid dehydrogenase in aldosterone target cells. J Biol Chem 268:10717-10720
107. Korbmacher C, Schulz W, Konig M, Siebe H, Lichtenstein I, Hierholzer K 1989 Renal epithelial cell lines (BSC-1, MDCK, LLC-PK1) express 11 beta-hydroxysteroid dehydrogenase activity. Biochim Biophys Acta 1010:311-317
108. Leckie C, Chapman KE, Edwards CR, Seckl JR 1995 LLC-PK1 cells model 11 beta-hydroxysteroid dehydrogenase type 2 regulation of glucocorticoid access to renal mineralocorticoid receptors. Endocrinology 136:5561-5569
109. Burton AF, Anderson FH 1983 Inactivation of corticosteroids in intestinal mucosa by 11 beta-hydroxysteroid: NADP oxidoreductase (EC 1.1.1.146). Am J Gastroenterol 78:627-631
110. Whorwood CB, Barber PC, Gregory J, Sheppard MC, Stewart PM 1993 11 Beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in the rat colon. Am J Physiol 264: E951-E957
111. Moisan MP, Seckl JR, Edwards CR 1990 11 Beta-hydroxysteroid dehydrogenase bioactivity and messenger RNA expression in rat forebrain: localization in hypothalamus, hippocampus, and cortex. Endocrinology 127:1450-1455
112. Lakshmi V, Sakai RR, McEwen BS, Monder C 1991 Regional distribution of 11 beta-hydroxysteroid dehydrogenase in rat brain. Endocrinology 128:1741-1748
113. Rajan V, Edwards CR, Seckl JR 1996 11β-Hydroxysteroid dehydrogenase in cultured hippocampal cells reactivates inert 11-dehydrocorticosterone, potentiating neurotoxicity. J Neurosci 16:65-70
114. McEwen BS, de Kloet ER, Rostene W 1986 Adrenal steroid receptors and action in the nervous system. Physiol Rev 66:1121-1188
115. Arriza JL, Simerly RB, Swanson LW, Evans RM 1988 The neuronal mineralocorticoid receptor as a mediator of glucocorticoid response. Neuron 1:887-900
116. Gomez Sanchez EP 1991 What is the role of the central nervous system in mineralocorticoid hypertension? Am J Hypertens 4:374-381
117. Saruta T, Suzuki H, Handa M, Igarashi Y, Kondo K, Senba S 1986 Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndrome. J Clin Endocrinol Metab 62:275-279
118. Kornel L, Kanamarlapudi N, Travers T, Taff DJ, Patel N, Chen C, Baum RM, Raynor WJ 1982 Studies of high affinity binding of mineralo- and glucocorticoids in rabbit aorta cytosol. J Steroid Biochem 16:245-264
119. Funder JW, Pearce PT, Smith R, Campbell J 1989 Vascular type I aldosterone binding sites are physiological mineralocorticoid receptors. Endocrinology 125:2224-2226
120. Kornel L 1994 Colocalization of 11 beta-hydroxysteroid dehydrogenase and mineralocorticoid receptors in cultured vascular smooth muscle cells. Am J Hypertens 7:100-103
121. Walker BR, Yau JL, Brett LP, Seckl JR, Monder C, Williams BC, Edwards CR 1991 11 Beta-hydroxysteroid dehydrogenase in vascular smooth muscle and heart: implications for cardiovascular responses to glucocorticoids. Endocrinology 129:3305-3312
122. Walker BR, Campbell JC, Williams BC, Edwards CR 1992 Tissue-specific distribution of the NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase. Endocrinology 131:970-972
123. Takeda Y, Miyamori I, Yoneda T, Iki K, Hatakeyama H, Takeda R 1994 Gene expression of 11 beta-hydroxysteroid dehydrogenase in the mesenteric arteries of genetically hypertensive rats. Hypertension 23:577-580
124. Brilla CG, Matsubara LS, Weber KT 1993 Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol 25:563-575
125. Young M, Fullerton MJ, Dilley R, Funder JW 1994 Mineralocorticoids, hypertension, and cardiac fibrosis. J Clin Invest 93:2578-2583
126. Lombes M, Alfaidy N, Eugene E, Lessana A, Farman N, Bonvalet JP 1995 Prerequisite for cardiac aldosterone action. Mineralocorticoid receptor and 11 beta-hydroxysteroid dehydrogenase in the human heart. Circulation 92:175-182
127. Kenouch S, Lombes M, Delahaye F, Eugene E, Bonvalet JP, Farman N 1994 Human skin as target for aldosterone: coexpression of mineralocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab 79:1334-1341
128. Hammami MM, Siiteri PK 1991 Regulation of 11 beta-hydroxysteroid dehydrogenase activity in human skin fibroblasts: enzymatic modulation of glucocorticoid action. J Clin Endocrinol Metab 73:326-334
129. Teelucksingh S, Mackie AD, Burt D, McIntyre MA, Brett L, Edwards CR 1990 Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet 335:1060-1063
130. Benediktsson R, Yau JL, Low S, Brett LP, Cooke BE, Edwards CR, Seckl JR 1992 11 beta-Hydroxysteroid dehydrogenase in the rat ovary: high expression in the oocyte. J Endocrinol 135:53-58
131. Michael AE, Gregory L, Walker SM, Antoniw JW, Shaw RW, Edwards CR, Cooke BA 1993 Ovarian 11 beta-hydroxysteroid dehydrogenase: potential predictor of conception by in-vitro fertilisation and embryo transfer. Lancet 342:711-712
132. Michael AE, Gregory L, Piercy EC, Walker SM, Shaw RW, Cooke BA 1995 Ovarian 11 beta-hydroxysteroid dehydrogenase activity is inversely related to the outcome of in vitro fertilization-embryo transfer treatment cycles. Fertil Steril 64:590-598
133. Michael AE, Pester LA, Curtis P, Shaw RW, Edwards CR, Cooke BA 1993 Direct inhibition of ovarian steroidogenesis by Cortisol and the modulatory role of 11 beta-hydroxysteroid dehydrogenase. Clin Endocrinol (Oxf) 38:641-644
134. Beitins IZ, Bayard F, Ances IG, Kowarski A, Migeon CJ 1973 The metabolic clearance rate, blood production, interconversion and transplacental passage of cortisol and cortisone in pregnancy near term. Pediatr Res 7:509-519
135. Murphy BE, Clark SJ, Donald IR, Pinsky M, Vedady D 1974 Conversion of maternal cortisol to cortisone during placental transfer to the human fetus. Am J Obstet Gynecol 118:538-541
136. Arcuri F, Monder C, Lockwood CJ, Schatz F 1996 Expression of 11β-hydroxysteroid dehydrogenase during decidualization of human endometrial stromal cells. Endocrinology 137:595-600
137. Guller S, Wozniak R, Krikun G, Burnhan JM, Kaplan P, Lockwood CJ 1993 Glucocorticoid suppression of human placental fibronectin expression: implications in uterine-placental adherence. Endocrinology 133:1139-1146
138. Lakshmi V, Nath N, Muneyyirci-Delale O 1993 Characterization of 11 beta-hydroxysteroid dehydrogenase of human placenta: evidence for the existence of two species of 11 beta-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol 45:391-397
139. Brown RW, Chapman KE, Edwards CR, Seckl JR 1993 Human placental 11 beta-hydroxysteroid dehydrogenase: evidence for and partial purification of a distinct NAD-dependent isoform. Endocrinology 132:2614-2621
140. Gomez-Sanchez EP, Cox DL, Foecking MF, Ganjam VK, Gomez-Sanchez CE 1996 11β-Hydroxysteroid dehydrogenases of the choriocarcinoma cell line JEG-3 and their inhibition by glycyrrhetinic acid and other natural substances. Steroids 61:110-115
141. Baggia S, Albrecht ED, Pepe GJ 1990 Regulation of 11 beta-hydroxysteroid dehydrogenase activity in the baboon placenta by estrogen. Endocrinology 126:2742-2748
142. Baggia S, Albrecht ED, Babischkin JS, Pepe GJ 1990 Interconversion of cortisol and cortisone in baboon trophoblast and decidua cells in culture. Endocrinology 127:1735-1741
143. Murphy BE 1981 Ontogeny of cortisol-cortisone interconversion in human tissues: a role for cortisone in human fetal development. J Steroid Biochem 14:811-817
144. Smith BT, Torday JS, Giroud CJ 1973 The growth promoting effect of cortisol on human fetal lung cells. Steroids 22:515-524
145. Torday JS, Post M, Smith BT 1985 Compartmentalization of 11-oxidoreductase within fetal lung alveolus. Am J Physiol 249:C173-C176
146. Lakshmi V, Monder C 1985 Extraction of 11 beta-hydroxysteroid dehydrogenase from rat liver microsomes by detergents. J Steroid Biochem 22:331-340
147. Lakshmi V, Monder C 1985 Evidence for independent 11-oxidase and 11-reductase activities of 11 beta-hydroxysteroid dehydrogenase: enzyme latency, phase transitions, and lipid requirements. Endocrinology 116:552-560
148. Ghosh D, Weeks CM, Grochulski P, Duax WL, Erman M, Rimsay RL, Orr JC 1991 Three-dimensional structure of holo 3 alpha,20 beta-hydroxysteroid dehydrogenase: a member of a short-chain dehydrogenase family. Proc Natl Acad Sci USA 88:10064-10068
149. Ozols J 1995 Lumenal orientation and post-translational modifications of the liver microsomal 11 beta-hydroxysteroid dehydrogenase. J Biol Chem 270:2305-2312
150. Agarwal AK, Monder C, Eckstein B, White PC 1989 Cloning and expression of rat cDNA encoding corticosteroid 11 beta-dehydrogenase. J Biol Chem 264:18939-18943
151. Tannin GM, Agarwal AK, Monder C, New MI, White PC 1991 The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. J Biol Chem 266:16653-16658
152. Rajan V, Chapman KE, Lyons V, Jamieson P, Mullins JJ, Edwards CR, Seckl JR 1995 Cloning, sequencing and tissue-distribution of mouse 11 beta-hydroxysteroid dehydrogenase-1 cDNA. J Steroid Biochem Mol Biol 52:141-147
153. Yang K, Smith CL, Dales D, Hammond GL, Challis JR 1992 Cloning of an ovine 11 beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid: tissue and temporal distribution of its messenger ribonucleic acid during fetal and neonatal development. Endocrinology 131:2120-2126
154. Moore CC, Mellon SH, Murai J, Siiteri PK, Miller WL 1993 Structure and function of the hepatic form of 11 beta-hydroxysteroid dehydrogenase in the squirrel monkey, an animal model of glucocorticoid resistance. Endocrinology 133:368-375
155. Persson B, Krook M, Jornvall H 1991 Characteristics of short-chain alcohol dehydrogenases and related enzymes. Eur J Biochem 200: 537-543
156. Obeid J, White PC 1992 Tyr-179 and Lys-183 are essential for enzymatic activity of 11 beta-hydroxysteroid dehydrogenase. Biochem Biophys Res Commun 188:222-227
157. Ensor CM, Tai HH 1993 Site-directed mutagenesis of the conserved tyrosine-151 of human placental NAD+-dependent 15-hydroxyprostaglandin dehydrogenase yields a catalytically inactive enzyme. Biochem Biophys Res Commun 176:840-845
158. Chen Z, Jiang JC, Lin ZG, Lee WR, Baker ME, Chang SH 1993 Site-specific mutagenesis of Drosophila alcohol dehydrogenase: evidence for involvement of tyrosine-152 and lysine-156 in catalysis. Biochemistry 32:3342-3346
159. Ghosh D, Erman M, Pangborn W, Duax WL, Baker ME 1992 Inhibition of Streptomyces hydrogenans 3 alpha,20 beta-hydroxysteroid dehydrogenase by licorice-derived compounds and crystallization of an enzyme-cofactor-inhibitor complex. J Steroid Biochem Mol Biol 42:849-853
160. Obeid J, Curnow KM, Aisenberg J, White PC 1993 Transcripts originating in intron 1 of the HSD11 (11 beta-hydroxysteroid dehydrogenase) gene encode a truncated polypeptide that is enzymatically inactive. Mol Endocrinol 7:154-160
161. Agarwal AK, Tusie-Luna MT, Monder C, White PC 1990 Expression of 11 beta-hydroxysteroid dehydrogenase using recombinant vaccinia virus. Mol Endocrinol 4:1827-1832
162. Low SC, Chapman KE, Edwards CR, Seckl JR 1994 'Liver-type' 11 beta-hydroxysteroid dehydrogenase cDNA encodes reductase but not dehydrogenase activity in intact mammalian COS-7 cells. J Mol Endocrinol 13:167-174
163. Duperrex H, Kenouch S, Gaeggeler HP, Seckl JR, Edwards CR, Farman N, Rossier BC 1993 Rat liver 11 beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid encodes oxoreductase activity in a mineralocorticoid-responsive toad bladder cell line. Endocrinology 132:612-619
164. Agarwal AK, Mune T, Monder C, White PC 1995 Mutations in putative glycosylation sites of rat 11 beta-hydroxysteroid dehydrogenase affect enzymatic activity. Biochim Biophys Acta 1248: 70-74
165. Krozowski Z, Stuchbery S, White P, Monder C, Funder JW 1990 Characterization of 11 beta-hydroxysteroid dehydrogenase gene expression: identification of multiple unique forms of messenger ribonucleic acid in the rat kidney. Endocrinology 127:3009-3013
166. Monder C, Lakshmi V 1990 Corticosteroid 11 beta-dehydrogenase of rat tissues: immunological studies. Endocrinology 126:2435-2443
167. Whorwood CB, Franklyn JA, Sheppard MC, Stewart PM 1992 Tissue localization of 11 beta-hydroxysteroid dehydrogenase and its relationship to the glucocorticoid receptor. J Steroid Biochem Mol Biol 41:21-28
168. Krozowski Z, Obeyesekere V, Smith R, Mercer W 1992 Tissue-specific expression of an 11 beta-hydroxysteroid dehydrogenase with a truncated N-terminal domain. A potential mechanism for differential intracellular localization within mineralocorticoid target cells. J Biol Chem 267:2569-2574
169. Moisan MP, Edwards CR, Seckl JR 1992 Differential promoter usage by the rat 11 beta-hydroxysteroid dehydrogenase gene. Mol Endocrinol 6:1082-1087
170. Mercer W, Obeyesekere V, Smith R, Krozowski Z 1993 Characterization of 11 beta-HSD1B gene expression and enzymatic activity. Mol Cell Endocrinol 92:247-251
171. Rundle SE, Funder JW, Lakshmi V, Monder C 1989 The intrarenal localization of mineralocorticoid receptors and 11 beta-dehydrogenase: immunocytochemical studies. Endocrinology 125:1700-1704
172. Castello R, Schwarting R, Muller C, Hierholzer K 1989 Immunohistochemical localization of 11-hydroxysteroid dehydrogenase in rat kidney with monoclonal antibody. Renal Physiol Biochem 12:320-327
173. Stewart PM, Whorwood CB, Barber P, Gregory J, Monder C, Franklyn JA, Sheppard MC 1991 Localization of renal 11 beta-dehydrogenase by in situ hybridization: autocrine not paracrine protector of the mineralocorticoid receptor. Endocrinology 128: 2129-2135
174. Yau JL, Van Haarst AD, Moisan MP, Fleming S, Edwards CR, Seckl JR 1991 11 beta-Hydroxysteroid dehydrogenase mRNA expression in rat kidney. Am J Physiol 260:F764-F767
175. Phillips DM, Lakshmi V, Monder C 1989 Corticosteroid 11 beta-dehydrogenase in rat testis. Endocrinology 125:209-216
176. Low SC, Chapman KE, Edwards CR, Wells T, Robinson IC, Seckl JR 1994 Sexual dimorphism of hepatic 11 beta-hydroxysteroid dehydrogenase in the rat: the role of growth hormone patterns. J Endocrinol 143:541-548
177. Albiston AL, Smith RE, Krozowski ZS 1995 Sex- and tissue-specific regulation of 11 beta-hydroxysteroid dehydrogenase mRNA. Mol Cell Endocrinol 109:183-188
178. Low SC, Assaad SN, Rajan V, Chapman KE, Edwards CR, Seckl JR 1993 Regulation of 11 beta-hydroxysteroid dehydrogenase by sex steroids in vivo: further evidence for the existence of a second dehydrogenase in rat kidney. J Endocrinol 139:27-35
179. Yang K, Berdusco ET, Challis JR 1994 Opposite effects of glucocorticoid on hepatic 11 beta-hydroxysteroid dehydrogenase mRNA and activity in fetal and adult sheep. J Endocrinol 143:121-126
180. Page N, Warriar N, Govindan MV 1994 11 beta-hydroxysteroid dehydrogenase activity in human lung cells and transcription regulation by glucocorticoids. Am J Physiol 267:L464-474
181. Mercer WR, Krozowski ZS 1992 Localization of an 11 beta hydroxysteroid dehydrogenase activity to the distal nephron. Evidence for the existence of two species of dehydrogenase in the rat kidney. Endocrinology 130:540-543
182. Yang K, Yu M 1994 Evidence for distinct isoforms of 11-beta-hydroxysteroid dehydrogenase in the ovine liver and kidney. J Steroid Biochem Mol Biol 49:245-250
183. Stewart PM, Murry BA, Mason JI 1994 Type 2 11beta-hydroxysteroid dehydrogenase in human fetal tissues. J Clin Endocrinol Metab 78:1529-1532
184. Brown RW, Chapman KE, Murad P, Edwards CR, Seckl JR 1996 Purification of 11β-hydroxysteroid dehydrogenase type 2 from human placenta utilizing a novel affinity labelling technique. Biochem J 313:997-1005
185. Agarwal AK, Mune T, Monder C, White PC 1994 NAD+-dependent isoform of 11 beta hydroxysteroid dehydrogenase:cloning and characterization of cDNA from sheep kidney. J Biol Chem 269: 25959-25962
186. Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS 1994 Cloning and tissue distribution of the human 11-HSD type 2 enzyme. Mol Cell Endocrinol 105:R11-R17
187. Naray-Fejes-Toth A, Fejes-Toth G 1995 Expression cloning of the aldosterone target cell-specific 11 beta-hydroxysteroid dehydrogenase from rabbit collecting duct cells. Endocrinology 136:2579-2586
188. Zhou MY, Gomez-Sanchez EP, Cox DL, Cosby D, Gomez-Sanchez CE 1995 Cloning, expression, and tissue distribution of the rat nicotinamide adenine dinucleotide-dependent 11 beta-hydroxysteroid dehydrogenase. Endocrinology 136:3729-3734
189. Cole TJ 1995 Cloning of the mouse 11 beta-hydroxysteroid dehydrogenase type 2 gene: tissue specific expression and localization in distal convoluted tubules and collecting ducts of the kidney. Endocrinology 136:4693-4696
190. Wu L, Einstein M, Geissler WM, Chan HC, Elliston KO, Andersson S 1993 Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity. J Biol Chem 268:12964-12969
191. Agarwal AK, Rogerson FM, Mune T, White PC 1995 Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (type 2) isozyme of 11β-hydroxysteroid dehydrogenase. Genomics 29:195-199
192. Agarwal AK, White PC 1996 Analysis of the promoter of the NAD+ dependent 11β-hydroxysteroid dehydrogenase (HSD11K) gene in JEG-3 human choriocarcinoma cells. Mol Cell Endocrinol 121:93-99
193. Casey ML, MacDonald PC, Andersson S 1994 17-HSD type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium. J Clin Invest 94:2135-2141
194. Roland BL, Krozowski ZS, Funder JW 1995 Glucocorticoid receptor, mineralocorticoid receptors, 11 beta-hydroxysteroid dehydrogenase-1 and -2 expression in rat brain and kidney: in situ studies. Mol Cell Endocrinol 111: R1-7
195. Whorwood CB, Mason JI, Ricketts ML, Howie AJ, Stewart PM 1995 Detection of human 11 beta-hydroxysteroid dehydrogenase isoforms using reverse-transcriptase-polymerase chain reaction and localization of the type 2 isoform to renal collecting ducts. Mol Cell Endocrinol 110:R7-12
196. Krozowski Z, MaGuire JA, Stein-Oakley AN, Dowling J, Smith RE, Andrews RK 1995 Immunohistochemical localization of the 11 beta-hydroxysteroid dehydrogenase type II enzyme in human kidney and placenta. J Clin Endocrinol Metab 80:2203-2209
197. Kyossev Z, Walker PD, Reeves WB 1996 Immunolocalization of NAD-dependent 11β-hydroxysteroid dehydrogenase in human kidney and colon. Kidney Int 49:271-281
198. Roland BL, Funder JW 1996 Localization of 11β-hydroxysteroid dehydrogenase type 2 in rat tissues: in situ studies. Endocrinology 137:1123-1128
199. Yang K, Matthews SG 1995 Cellular localization of 11 beta-hydroxysteroid dehydrogenase 2 gene expression in the ovine adrenal gland. Mol Cell Endocrinol 111:R19-23
200. Roland BL, Li KX, Funder JW 1995 Hybridization histochemical localization of 11 beta-hydroxysteroid dehydrogenase type 2 in rat brain. Endocrinology 136:4697-4700
201. Brown RW, Diaz R, Robson AC, Kotelevtsev YV, Mullins JJ, Kaufman M, Seekl JR 1996 The ontogeny of 11β-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Endocrinology 137:794-797
202. Stewart PM, Krozowski ZS, Gupta A, Milford DV, Howie AJ, Sheppard MC, Whorwood CB 1996 Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation of the 11β-hydroxysteroid dehydrogenase type 2 gene. Lancet 347:88-91
203. Mune T, White PC 1996 Apparent mineralocorticoid excess: genotype is correlated with biochemical phenotype. Hypertension 27:1193-1199
204. Wilson TW, Grim CE 1991 Biohistory of slavery and blood pressure differences in blacks today: a hypothesis. Hypertension 17: 1122-1128
205. Obeyesekere VR, Ferrari P, Andrews RK, Wilson RC, New MI, Funder JW, Krozowski ZS 1995 The R337C mutation generates a high Km 11β-hydroxysteroid dehydrogenase type II enzyme in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab 80:3381-3383
206. Tusie-Luna MT, Traktman P, White PC 1990 Determination of functional effects of mutations in the steroid 21-hydroxylase gene (CYP21) using recombinant vaccinia virus, J Biol Chem 265:20916-20922
207. Gruol DJ, Bourgeois S 1994 Expression of the mdr1 P-glycoprotein gene: a mechanism of escape from glucocorticoid-induced apoptosis. Biochem Cell Biol 72:561-571
208. Speiser PW, Dupont J, Zhu D, Serrat J, Buegeleisen M, Tusie-Luna MT, Lesser M, New MI, White PC 1992 Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Invest 90:584-595
209. Lifton RP 1995 Genetic determinants of human hypertension. Proc Natl Acad Sci USA 92:8545-8551
210. Smithies O, Kim HS 1994 Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice. Proc Natl Acad Sci USA 91:3612-3615