11ß-Hydroxysteroid Dehydrogenase and the Syndrome of Apparent Mineralocorticoid Excess1
Perrin C. White,
Tomoatsu Mune2 and
Anil K. Agarwal
Department of Pediatrics, University of Texas Southwestern Medical
Center, Dallas Texas 75235-9063
I. Introduction
II. Biochemistry of Cortisol Metabolism
III.Mineralocorticoid Receptor Function
A. Actions of aldosterone
B. Structure and function of the mineralocorticoid receptor
C. Hypothesis: 11-HSD protects the mineralocorticoid receptor
IV. Loss of Function of 11-HSD
A. Syndrome of apparent mineralocorticoidexcess (AME)
B. Licorice intoxication
C. Ectopic ACTH syndrome
D. Essential hypertension
E. Related conditions
V. FunctionalRoles of 11-HSD
A. Liver
B. Kidney and other mineralocorticoidtarget tissues
C. Brain
D. Circulatory system
E. Skin
F. Ovary
G. Placenta
H. Other fetal tissues
VI. TheType I (Liver) Isozyme of 11-HSD
A. Terminology
B. Biochemistry
C. Molecular biology
D. Expression
E. Lack of involvementin the syndromes of AME or 11-reductasedeficiency
VII. TheType 2 (Kidney) Isozyme of 11-HSD
A. Biochemistry
B. Molecularbiology
C. Expression
D. Mutations in HSD11B2 are detectedin all patients with AME
VIII. Summary\.
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B. S. Nunez, F. M. Rogerson, T. Mune, Y. Igarashi, Y. Nakagawa, G. Phillipov, A. Moudgil, L. B. Travis, M. Palermo, C. Shackleton, et al. Mutants of 11{beta}-Hydroxysteroid Dehydrogenase (11-HSD2) With Partial Activity : Improved Correlations Between Genotype and Biochemical Phenotype in Apparent Mineralocorticoid Excess
Hypertension,
October 1, 1999;
34(4):
638 - 642.
[Abstract][Full Text][PDF]
I. J. Bujalska, S. Kumar, M. Hewison, and P. M. Stewart Differentiation of Adipose Stromal Cells: The Roles of Glucocorticoids and 11{beta}-Hydroxysteroid Dehydrogenase
Endocrinology,
July 1, 1999;
140(7):
3188 - 3196.
[Abstract][Full Text]
D.B. Hardy, L.E. Pereria, and K. Yang Prostaglandins and Leukotriene B4 Are Potent Inhibitors of 11ß-Hydroxysteroid Dehydrogenase Type 2 Activity in Human Choriocarcinoma JEG-3 Cells
Biol Reprod,
July 1, 1999;
61(1):
40 - 45.
[Abstract][Full Text]
E. P. Gomez-Sanchez and C. E. Gomez-Sanchez Maternal Hypertension and Progeny Blood Pressure : Role of Aldosterone and 11ß-HSD
Hypertension,
June 1, 1999;
33(6):
1369 - 1373.
[Abstract][Full Text][PDF]
R.-S. Ge, D. O. Hardy, J. F. Catterall, and M. P. Hardy Opposing Changes in 3{alpha}-Hydroxysteroid Dehydrogenase Oxidative and Reductive Activities in Rat Leydig Cells during Pubertal Development
Biol Reprod,
April 1, 1999;
60(4):
855 - 860.
[Abstract][Full Text]
P. M. Stewart, A. Boulton, S. Kumar, P. M. S. Clark, and C. H. L. Shackleton Cortisol Metabolism in Human Obesity: Impaired Cortisone->Cortisol Conversion in Subjects with Central Adiposity
J. Clin. Endocrinol. Metab.,
March 1, 1999;
84(3):
1022 - 1027.
[Abstract][Full Text]
F. E. Brennan and P. J. Fuller Acute Regulation by Corticosteroids of Channel-Inducing Factor Gene Messenger Ribonucleic Acid in the Distal Colon
Endocrinology,
March 1, 1999;
140(3):
1213 - 1218.
[Abstract][Full Text]
J. Tremblay, D.B. Hardy, L.E. Pereira, and K. Yang Retinoic Acid Stimulates the Expression of 11ß-Hydroxysteroid Dehydrogenase Type 2 in Human Choriocarcinoma JEG-3 Cells
Biol Reprod,
March 1, 1999;
60(3):
541 - 545.
[Abstract][Full Text]
P. J. Burton and B. J. Waddell Dual Function of 11ß-Hydroxysteroid Dehydrogenase in Placenta: Modulating Placental Glucocorticoid Passage and Local Steroid Action
Biol Reprod,
February 1, 1999;
60(2):
234 - 240.
[Abstract][Full Text][PDF]
M. Tetsuka, M. Milne, G.E. Simpson, and S.G. Hillier Expression of 11ß-Hydroxysteroid Dehydrogenase, Glucocorticoid Receptor, and Mineralocorticoid Receptor Genes in Rat Ovary
Biol Reprod,
February 1, 1999;
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330 - 335.
[Abstract][Full Text][PDF]
D. Rogoff, Z. Smolenicka, I. Bergadá, G. Vallejo, M. Barontini, J. J. Heinrich, and P. Ferrari The Codon 213 of the 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Gene Is a Hot Spot for Mutations in Apparent Mineralocorticoid Excess
J. Clin. Endocrinol. Metab.,
December 1, 1998;
83(12):
4391 - 4393.
[Abstract][Full Text]
J. Condon, C. Gosden, D. Gardener, P. Nickson, M. Hewison, A. J. Howie, and P. M. Stewart Expression of Type 2 11{beta}-Hydroxysteroid Dehydrogenase and Corticosteroid Hormone Receptors in Early Human Fetal Life
J. Clin. Endocrinol. Metab.,
December 1, 1998;
83(12):
4490 - 4497.
[Abstract][Full Text]
R. Sampath-Kumar, S.G. Matthews, and K. Yang 11ß-Hydroxysteroid Dehydrogenase Type 2 Is the Predominant Isozyme in the Guinea Pig Placenta: Decreases in Messenger Ribonucleic Acid and Activity at Term
Biol Reprod,
December 1, 1998;
59(6):
1378 - 1384.
[Abstract][Full Text]
G. Mazzocchi, G. P. Rossi, G. Neri, L. K. Malendowicz, G. Albertin, and G. G. Nussdorfer 11ß-Hydroxysteroid dehydrogenase expression and activity in the human adrenal cortex
FASEB J,
November 1, 1998;
12(14):
1533 - 1539.
[Abstract][Full Text]
D. Fuster, G. Escher, B. Vogt, D. Ackermann, B. Dick, B. M. Frey, and F. J. Frey Furosemide Inhibits 11{beta}-Hydroxysteroid Dehydrogenase Type 2
Endocrinology,
September 1, 1998;
139(9):
3849 - 3854.
[Abstract][Full Text][PDF]
R. Diaz, R. W. Brown, and J. R. Seckl Distinct Ontogeny of Glucocorticoid and Mineralocorticoid Receptor and 11beta -Hydroxysteroid Dehydrogenase Types I and II mRNAs in the Fetal Rat Brain Suggest a Complex Control of Glucocorticoid Actions
J. Neurosci.,
April 1, 1998;
18(7):
2570 - 2580.
[Abstract][Full Text][PDF]
E. P. Gomez-Sanchez Editorial: First There Was One, Then Two . . . Why More 11{beta}-Hydroxysteroid Dehydrogenases?
Endocrinology,
December 1, 1997;
138(12):
5087 - 5088.
[Full Text][PDF]
R.-S. Ge, D. O. Hardy, J. F. Catterall, and M. P. Hardy Developmental Changes in Glucocorticoid Receptor and 11{beta}-Hydroxysteroid Dehydrogenase Oxidative and Reductive Activities in Rat Leydig Cells
Endocrinology,
December 1, 1997;
138(12):
5089 - 5095.
[Abstract][Full Text][PDF]
A. Odermatt, P. Arnold, and F. J. Frey The Intracellular Localization of the Mineralocorticoid Receptor Is Regulated by 11beta -Hydroxysteroid Dehydrogenase Type 2
J. Biol. Chem.,
July 20, 2001;
276(30):
28484 - 28492.
[Abstract][Full Text][PDF]
J. L. W. Yau, J. Noble, C. J. Kenyon, C. Hibberd, Y. Kotelevtsev, J. J. Mullins, and J. R. Seckl Lack of tissue glucocorticoid reactivation in 11beta -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments
PNAS,
April 10, 2001;
98(8):
4716 - 4721.
[Abstract][Full Text][PDF]
J. Hanafusa, T. Mune, T. Tanahashi, Y. Isomura, T. Suwa, M. Isaji, H. Daido, H. Morita, M. Murayama, and K. Yasuda Altered corticosteroid metabolism differentially affects pituitary corticotropin response
Am J Physiol Endocrinol Metab,
February 1, 2002;
282(2):
E466 - E473.
[Abstract][Full Text][PDF]
