The interconversion of active and inactive corticosteroids – cortisol and cortisone, respectively, in humans – is modulated by isozymes of 11β-hydroxysteroid dehydrogenase (11-HSD). Studies of this process have provided crucial insights into glucocorticoid effects in a wide variety of tissues. The 11-HSD1 isozyme functions mainly as an oxoreductase (cortisone to cortisol) and is expressed at high levels in the liver and other glucocorticoid target tissues. Because it is required for full physiological effects of cortisol, it has emerged as a drug target for metabolic syndrome and type 2 diabetes. Mutations in the corresponding HSD11B1 gene, or in the H6PD gene encoding hexose-6-phosphate dehydrogenase (which supplies the NADPH required for the oxoreductase activity of 11-HSD1), cause apparent cortisone reductase deficiency, a rare syndrome of adrenocortical hyperactivity and hyperandrogenism. In contrast, the 11-HSD2 isozyme functions as a dehydrogenase (cortisol to cortisone) and is expressed mainly in mineralocorticoid target tissues, where it bars access of cortisol to the mineralocorticoid receptor. Mutations in the HSD11B2 gene encoding 11-HSD2 cause the syndrome of apparent mineralocorticoid excess, a severe form of familial hypertension. The role of this enzyme in the pathogenesis of common forms of low-renin hypertension remains uncertain.

1.
White
PC
,
Mune
T
,
Agarwal
AK
.
11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess
.
Endocr Rev
.
1997
Feb
;
18
(
1
):
135
56
.
[PubMed]
0163-769X
2.
Tomlinson
JW
,
Walker
EA
,
Bujalska
IJ
,
Draper
N
,
Lavery
GG
,
Cooper
MS
, et al
11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response
.
Endocr Rev
.
2004
Oct
;
25
(
5
):
831
66
.
[PubMed]
0163-769X
3.
Chapman
K
,
Holmes
M
,
Seckl
J
.
11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action
.
Physiol Rev
.
2013
Jul
;
93
(
3
):
1139
206
.
[PubMed]
0031-9333
4.
Odermatt
A
,
Klusonova
P.
11beta-Hydroxysteroid dehydrogenase 1: Regeneration of active glucocorticoids is only part of the story. J Steroid Biochem Mol Biol 2015 Jul;151:85-92. doi: . Epub;%
2014
Aug 23.:85-92.
5.
Zhang
J
,
Osslund
TD
,
Plant
MH
,
Clogston
CL
,
Nybo
RE
,
Xiong
F
, et al
Crystal structure of murine 11 beta-hydroxysteroid dehydrogenase 1: an important therapeutic target for diabetes
.
Biochemistry
.
2005
May
;
44
(
18
):
6948
57
.
[PubMed]
0006-2960
6.
Thomas
MP
,
Potter
BV
.
Crystal structures of 11β-hydroxysteroid dehydrogenase type 1 and their use in drug discovery
.
Future Med Chem
.
2011
Mar
;
3
(
3
):
367
90
.
[PubMed]
1756-8919
7.
Singh
S
,
Tice
C
.
Structure based design of 11β-HSD1 inhibitors
.
Curr Pharm Biotechnol
.
2010
Nov
;
11
(
7
):
779
91
.
[PubMed]
1389-2010
8.
Bird
AD
,
Greatorex
S
,
Reser
D
,
Lavery
GG
,
Cole
TJ
.
Hydroxysteroid dehydrogenase HSD1L is localised to the pituitary-gonadal axis of primates
.
Endocr Connect
.
2017
Oct
;
6
(
7
):
489
99
.
[PubMed]
2049-3614
9.
Masuzaki
H
,
Paterson
J
,
Shinyama
H
,
Morton
NM
,
Mullins
JJ
,
Seckl
JR
, et al
A transgenic model of visceral obesity and the metabolic syndrome
.
Science
.
2001
Dec
;
294
(
5549
):
2166
70
.
[PubMed]
0036-8075
10.
Paterson
JM
,
Morton
NM
,
Fievet
C
,
Kenyon
CJ
,
Holmes
MC
,
Staels
B
, et al
Metabolic syndrome without obesity: hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice
.
Proc Natl Acad Sci USA
.
2004
May
;
101
(
18
):
7088
93
.
[PubMed]
0027-8424
11.
Kotelevtsev
Y
,
Holmes
MC
,
Burchell
A
,
Houston
PM
,
Schmoll
D
,
Jamieson
P
, et al
11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress
.
Proc Natl Acad Sci USA
.
1997
Dec
;
94
(
26
):
14924
9
.
[PubMed]
0027-8424
12.
Morgan
SA
,
McCabe
EL
,
Gathercole
LL
,
Hassan-Smith
ZK
,
Larner
DP
,
Bujalska
IJ
, et al
11β-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess
.
Proc Natl Acad Sci USA
.
2014
Jun
;
111
(
24
):
E2482
91
.
[PubMed]
0027-8424
13.
Engeli
S
,
Böhnke
J
,
Feldpausch
M
,
Gorzelniak
K
,
Heintze
U
,
Janke
J
, et al
Regulation of 11beta-HSD genes in human adipose tissue: influence of central obesity and weight loss
.
Obes Res
.
2004
Jan
;
12
(
1
):
9
17
.
[PubMed]
1071-7323
14.
Paulsen
SK
,
Pedersen
SB
,
Fisker
S
,
Richelsen
B
.
11Beta-HSD type 1 expression in human adipose tissue: impact of gender, obesity, and fat localization
.
Obesity (Silver Spring)
.
2007
Aug
;
15
(
8
):
1954
60
.
[PubMed]
1930-7381
15.
Desbriere
R
,
Vuaroqueaux
V
,
Achard
V
,
Boullu-Ciocca
S
,
Labuhn
M
,
Dutour
A
, et al
11beta-hydroxysteroid dehydrogenase type 1 mRNA is increased in both visceral and subcutaneous adipose tissue of obese patients
.
Obesity (Silver Spring)
.
2006
May
;
14
(
5
):
794
8
.
[PubMed]
1930-7381
16.
Tomlinson
JW
,
Sinha
B
,
Bujalska
I
,
Hewison
M
,
Stewart
PM
.
Expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue is not increased in human obesity
.
J Clin Endocrinol Metab
.
2002
Dec
;
87
(
12
):
5630
5
.
[PubMed]
0021-972X
17.
Lutz
SZ
,
Peter
A
,
Machicao
F
,
Lamprinou
A
,
Machann
J
,
Schick
F
, et al
Genetic Variation in the 11β-hydroxysteroid-dehydrogenase 1 Gene Determines NAFLD and Visceral Obesity
.
J Clin Endocrinol Metab
.
2016
Dec
;
101
(
12
):
4743
51
.
[PubMed]
0021-972X
18.
Moon
SS
,
Lee
YS
,
Kim
JG
,
Lee
IK
.
Association of 11β-hydroxysteroid dehydrogenase type 1 gene polymorphisms with serum alanine aminotransferase activity
.
Diabetes Res Clin Pract
.
2013
Mar
;
99
(
3
):
343
50
.
[PubMed]
0168-8227
19.
Tahrani
AA
,
Bailey
CJ
,
Del Prato
S
,
Barnett
AH
.
Management of type 2 diabetes: new and future developments in treatment
.
Lancet
.
2011
Jul
;
378
(
9786
):
182
97
.
[PubMed]
0140-6736
20.
Gathercole
LL
,
Lavery
GG
,
Morgan
SA
,
Cooper
MS
,
Sinclair
AJ
,
Tomlinson
JW
, et al
11β-Hydroxysteroid dehydrogenase 1: translational and therapeutic aspects
.
Endocr Rev
.
2013
Aug
;
34
(
4
):
525
55
.
[PubMed]
0163-769X
21.
Scott
JS
,
Goldberg
FW
,
Turnbull
AV
.
Medicinal chemistry of inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)
.
J Med Chem
.
2014
Jun
;
57
(
11
):
4466
86
.
[PubMed]
0022-2623
22.
Rosenstock
J
,
Banarer
S
,
Fonseca
VA
,
Inzucchi
SE
,
Sun
W
,
Yao
W
, et al;
INCB13739-202 Principal Investigators
.
The 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy
.
Diabetes Care
.
2010
Jul
;
33
(
7
):
1516
22
.
[PubMed]
0149-5992
23.
Turban
S
,
Liu
X
,
Ramage
L
,
Webster
SP
,
Walker
BR
,
Dunbar
DR
, et al
Optimal elevation of β-cell 11β-hydroxysteroid dehydrogenase type 1 is a compensatory mechanism that prevents high-fat diet-induced β-cell failure
.
Diabetes
.
2012
Mar
;
61
(
3
):
642
52
.
[PubMed]
0012-1797
24.
Harno
E
,
Cottrell
EC
,
Yu
A
,
DeSchoolmeester
J
,
Gutierrez
PM
,
Denn
M
, et al
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors still improve metabolic phenotype in male 11β-HSD1 knockout mice suggesting off-target mechanisms
.
Endocrinology
.
2013
Dec
;
154
(
12
):
4580
93
.
[PubMed]
0013-7227
25.
Anderson
A
,
Walker
BR
.
11β-HSD1 inhibitors for the treatment of type 2 diabetes and cardiovascular disease
.
Drugs
.
2013
Sep
;
73
(
13
):
1385
93
.
[PubMed]
0012-6667
26.
Stomby
A
,
Andrew
R
,
Walker
BR
,
Olsson
T
.
Tissue-specific dysregulation of cortisol regeneration by 11βHSD1 in obesity: has it promised too much?
Diabetologia
.
2014
Jun
;
57
(
6
):
1100
10
.
[PubMed]
0012-186X
27.
Morgan
SA
,
Hassan-Smith
ZK
,
Lavery
GG
.
MECHANISMS IN ENDOCRINOLOGY: tissue-specific activation of cortisol in Cushing’s syndrome
.
Eur J Endocrinol
.
2016
Aug
;
175
(
2
):
R83
9
.
[PubMed]
0804-4643
28.
Dube
S
,
Slama
MQ
,
Basu
A
,
Rizza
RA
,
Basu
R
.
Glucocorticoid Excess Increases Hepatic 11β-HSD-1 Activity in Humans: Implications in Steroid-Induced Diabetes
.
J Clin Endocrinol Metab
.
2015
Nov
;
100
(
11
):
4155
62
.
[PubMed]
0021-972X
29.
Yuan
X
,
Li
H
,
Bai
H
,
Zhao
X
,
Zhang
C
,
Liu
H
, et al
The 11beta-hydroxysteroid dehydrogenase type 1 inhibitor protects against the insulin resistance and hepatic steatosis in db/db mice. Eur J Pharmacol 2016 Oct 5;788:140-151. doi: . Epub;%
2016
May 27.:140-51.
30.
Stefan
N
,
Ramsauer
M
,
Jordan
P
,
Nowotny
B
,
Kantartzis
K
,
Machann
J
, et al
Inhibition of 11β-HSD1 with RO5093151 for non-alcoholic fatty liver disease: a multicentre, randomised, double-blind, placebo-controlled trial
.
Lancet Diabetes Endocrinol
.
2014
May
;
2
(
5
):
406
16
.
[PubMed]
2213-8587
31.
Ahmed
A
,
Rabbitt
E
,
Brady
T
,
Brown
C
,
Guest
P
,
Bujalska
IJ
, et al
A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease
.
PLoS One
.
2012
;
7
(
2
):
e29531
.
[PubMed]
1932-6203
32.
Larner
DP
,
Morgan
SA
,
Gathercole
LL
,
Doig
CL
,
Guest
P
,
Weston
C
, et al
Male 11β-HSD1 Knockout Mice Fed Trans-Fats and Fructose Are Not Protected From Metabolic Syndrome or Nonalcoholic Fatty Liver Disease
.
Endocrinology
.
2016
Sep
;
157
(
9
):
3493
504
.
[PubMed]
0013-7227
33.
Clarke
JL
,
Mason
PJ
.
Murine hexose-6-phosphate dehydrogenase: a bifunctional enzyme with broad substrate specificity and 6-phosphogluconolactonase activity
.
Arch Biochem Biophys
.
2003
Jul
;
415
(
2
):
229
34
.
[PubMed]
0003-9861
34.
Bánhegyi
G
,
Benedetti
A
,
Fulceri
R
,
Senesi
S
.
Cooperativity between 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase in the lumen of the endoplasmic reticulum
.
J Biol Chem
.
2004
Jun
;
279
(
26
):
27017
21
.
[PubMed]
0021-9258
35.
Atanasov
AG
,
Nashev
LG
,
Schweizer
RA
,
Frick
C
,
Odermatt
A
.
Hexose-6-phosphate dehydrogenase determines the reaction direction of 11beta-hydroxysteroid dehydrogenase type 1 as an oxoreductase
.
FEBS Lett
.
2004
Jul
;
571
(
1-3
):
129
33
.
[PubMed]
0014-5793
36.
Bujalska
IJ
,
Draper
N
,
Michailidou
Z
,
Tomlinson
JW
,
White
PC
,
Chapman
KE
, et al
Hexose-6-phosphate dehydrogenase confers oxo-reductase activity upon 11 beta-hydroxysteroid dehydrogenase type 1
.
J Mol Endocrinol
.
2005
Jun
;
34
(
3
):
675
84
.
[PubMed]
0952-5041
37.
Zhang
YL
,
Zhong
X
,
Gjoka
Z
,
Li
Y
,
Stochaj
W
,
Stahl
M
, et al
H6PDH interacts directly with 11beta-HSD1: implications for determining the directionality of glucocorticoid catalysis
.
Arch Biochem Biophys
.
2009
Mar
;
483
(
1
):
45
54
.
[PubMed]
0003-9861
38.
Lavery
GG
,
Walker
EA
,
Draper
N
,
Jeyasuria
P
,
Marcos
J
,
Shackleton
CH
, et al
Hexose-6-phosphate dehydrogenase knock-out mice lack 11 beta-hydroxysteroid dehydrogenase type 1-mediated glucocorticoid generation
.
J Biol Chem
.
2006
Mar
;
281
(
10
):
6546
51
.
[PubMed]
0021-9258
39.
Walker
EA
,
Ahmed
A
,
Lavery
GG
,
Tomlinson
JW
,
Kim
SY
,
Cooper
MS
, et al
11beta-Hydroxysteroid Dehydrogenase Type 1 Regulation by Intracellular Glucose 6-Phosphate Provides Evidence for a Novel Link between Glucose Metabolism and Hypothalamo-Pituitary-Adrenal Axis Function
.
J Biol Chem
.
2007
Sep
;
282
(
37
):
27030
6
.
[PubMed]
0021-9258
40.
Rogoff
D
,
Ryder
JW
,
Black
K
,
Yan
Z
,
Burgess
SC
,
McMillan
DR
, et al
Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase
.
Endocrinology
.
2007
Oct
;
148
(
10
):
5072
80
.
[PubMed]
0013-7227
41.
Lavery
GG
,
Hauton
D
,
Hewitt
KN
,
Brice
SM
,
Sherlock
M
,
Walker
EA
, et al
Hypoglycemia with enhanced hepatic glycogen synthesis in recombinant mice lacking hexose-6-phosphate dehydrogenase
.
Endocrinology
.
2007
Dec
;
148
(
12
):
6100
6
.
[PubMed]
0013-7227
42.
Lavery
GG
,
Walker
EA
,
Turan
N
,
Rogoff
D
,
Ryder
JW
,
Shelton
JM
, et al
Deletion of hexose-6-phosphate dehydrogenase activates the unfolded protein response pathway and induces skeletal myopathy
.
J Biol Chem
.
2008
Mar
;
283
(
13
):
8453
61
.
[PubMed]
0021-9258
43.
Jamieson
A
,
Wallace
AM
,
Andrew
R
,
Nunez
BS
,
Walker
BR
,
Fraser
R
, et al
Apparent cortisone reductase deficiency: a functional defect in 11beta-hydroxysteroid dehydrogenase type 1
.
J Clin Endocrinol Metab
.
1999
Oct
;
84
(
10
):
3570
4
.
[PubMed]
0021-972X
44.
Lawson
AJ
,
Walker
EA
,
Lavery
GG
,
Bujalska
IJ
,
Hughes
B
,
Arlt
W
, et al
Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1
.
Proc Natl Acad Sci USA
.
2011
Mar
;
108
(
10
):
4111
6
.
[PubMed]
0027-8424
45.
Draper
N
,
Walker
EA
,
Bujalska
IJ
,
Tomlinson
JW
,
Chalder
SM
,
Arlt
W
, et al
Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency
.
Nat Genet
.
2003
Aug
;
34
(
4
):
434
9
.
[PubMed]
1061-4036
46.
White
PC
.
Genotypes at 11beta-hydroxysteroid dehydrogenase type 11B1 and hexose-6-phosphate dehydrogenase loci are not risk factors for apparent cortisone reductase deficiency in a large population-based sample
.
J Clin Endocrinol Metab
.
2005
Oct
;
90
(
10
):
5880
3
.
[PubMed]
0021-972X
47.
Smit
P
,
Dekker
MJ
,
de Jong
FJ
,
van den Beld
AW
,
Koper
JW
,
Pols
HA
, et al
Lack of Association of the 11beta-hydroxysteroid dehydrogenase type 1 gene 83,557insA and hexose-6-phosphate dehydrogenase gene R453Q polymorphisms with body composition, adrenal androgen production, blood pressure, glucose metabolism, and dementia
.
J Clin Endocrinol Metab
.
2007
Jan
;
92
(
1
):
359
62
.
[PubMed]
0021-972X
48.
Lavery
GG
,
Walker
EA
,
Tiganescu
A
,
Ride
JP
,
Shackleton
CH
,
Tomlinson
JW
, et al
Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency
.
J Clin Endocrinol Metab
.
2008
Oct
;
93
(
10
):
3827
32
.
[PubMed]
0021-972X
49.
Qin
K
,
Rosenfield
RL
.
Mutations of the hexose-6-phosphate dehydrogenase gene rarely cause hyperandrogenemic polycystic ovary syndrome
.
Steroids
.
2011
Jan
;
76
(
1-2
):
135
9
.
[PubMed]
0039-128X
50.
Gomez-Sanchez
E
,
Gomez-Sanchez
CE
.
The multifaceted mineralocorticoid receptor
.
Compr Physiol
.
2014
Jul
;
4
(
3
):
965
94
.
[PubMed]
2040-4603
51.
Wyrwoll
CS
,
Holmes
MC
,
Seckl
JR
.
11β-hydroxysteroid dehydrogenases and the brain: from zero to hero, a decade of progress
.
Front Neuroendocrinol
.
2011
Aug
;
32
(
3
):
265
86
.
[PubMed]
0091-3022
52.
Cucca
F
,
Goy
JV
,
Kawaguchi
Y
,
Esposito
L
,
Merriman
ME
,
Wilson
AJ
, et al
A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3-positive patients
.
Nat Genet
.
1998
Jul
;
19
(
3
):
301
2
.
[PubMed]
1061-4036
53.
Dave-Sharma
S
,
Wilson
RC
,
Harbison
MD
,
Newfield
R
,
Azar
MR
,
Krozowski
ZS
, et al
Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess
.
J Clin Endocrinol Metab
.
1998
Jul
;
83
(
7
):
2244
54
.
[PubMed]
0021-972X
54.
Li
A
,
Tedde
R
,
Krozowski
ZS
,
Pala
A
,
Li
KX
,
Shackleton
CH
, et al
Molecular basis for hypertension in the “type II variant” of apparent mineralocorticoid excess
.
Am J Hum Genet
.
1998
Aug
;
63
(
2
):
370
9
.
[PubMed]
0002-9297
55.
Nunez
BS
,
Rogerson
FM
,
Mune
T
,
Igarashi
Y
,
Nakagawa
Y
,
Phillipov
G
, et al
Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess
.
Hypertension
.
1999
Oct
;
34
(
4 Pt 1
):
638
42
.
[PubMed]
0194-911X
56.
Ugrasbul
F
,
Wiens
T
,
Rubinstein
P
,
New
MI
,
Wilson
RC
.
Prevalence of mild apparent mineralocorticoid excess in Mennonites
.
J Clin Endocrinol Metab
.
1999
Dec
;
84
(
12
):
4735
8
.
[PubMed]
0021-972X
57.
Odermatt
A
,
Dick
B
,
Arnold
P
,
Zaehner
T
,
Plueschke
V
,
Deregibus
MN
, et al
A mutation in the cofactor-binding domain of 11beta-hydroxysteroid dehydrogenase type 2 associated with mineralocorticoid hypertension
.
J Clin Endocrinol Metab
.
2001
Mar
;
86
(
3
):
1247
52
.
[PubMed]
0021-972X
58.
Carvajal
CA
,
Gonzalez
AA
,
Romero
DG
,
González
A
,
Mosso
LM
,
Lagos
ET
, et al
Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess
.
J Clin Endocrinol Metab
.
2003
Jun
;
88
(
6
):
2501
7
.
[PubMed]
0021-972X
59.
Lavery
GG
,
Ronconi
V
,
Draper
N
,
Rabbitt
EH
,
Lyons
V
,
Chapman
KE
, et al
Late-onset apparent mineralocorticoid excess caused by novel compound heterozygous mutations in the HSD11B2 gene
.
Hypertension
.
2003
Aug
;
42
(
2
):
123
9
.
[PubMed]
0194-911X
60.
Quinkler
M
,
Bappal
B
,
Draper
N
,
Atterbury
AJ
,
Lavery
GG
,
Walker
EA
, et al
Molecular basis for the apparent mineralocorticoid excess syndrome in the Oman population
.
Mol Cell Endocrinol
.
2004
Mar
;
217
(
1-2
):
143
9
.
[PubMed]
0303-7207
61.
Lin-Su
K
,
Zhou
P
,
Arora
N
,
Betensky
BP
,
New
MI
,
Wilson
RC
.
In vitro expression studies of a novel mutation delta299 in a patient affected with apparent mineralocorticoid excess
.
J Clin Endocrinol Metab
.
2004
May
;
89
(
5
):
2024
7
.
[PubMed]
0021-972X
62.
Morineau
G
,
Sulmont
V
,
Salomon
R
,
Fiquet-Kempf
B
,
Jeunemaître
X
,
Nicod
J
, et al
Apparent mineralocorticoid excess: report of six new cases and extensive personal experience
.
J Am Soc Nephrol
.
2006
Nov
;
17
(
11
):
3176
84
.
[PubMed]
1046-6673
63.
Atanasov
AG
,
Ignatova
ID
,
Nashev
LG
,
Dick
B
,
Ferrari
P
,
Frey
FJ
, et al
Impaired protein stability of 11beta-hydroxysteroid dehydrogenase type 2: a novel mechanism of apparent mineralocorticoid excess
.
J Am Soc Nephrol
.
2007
Apr
;
18
(
4
):
1262
70
.
[PubMed]
1046-6673
64.
Al-Harbi
T
,
Al-Shaikh
A
.
Apparent mineralocorticoid excess syndrome: report of one family with three affected children
.
J Pediatr Endocrinol Metab
.
2012
;
25
(
11-12
):
1083
8
.
[PubMed]
0334-018X
65.
Pizzolo
F
,
Friso
S
,
Morandini
F
,
Antoniazzi
F
,
Zaltron
C
,
Udali
S
, et al
Apparent Mineralocorticoid Excess by a Novel Mutation and Epigenetic Modulation by HSD11B2 Promoter Methylation
.
J Clin Endocrinol Metab
.
2015
Sep
;
100
(
9
):
E1234
41
.
[PubMed]
0021-972X
66.
Alzahrani
AS
,
Aljuhani
N
,
Qasem
E
,
Almohanna
M
,
Hamoudh
E
,
AlOmair
A
, et al
Apparent Mineralocorticoid Excess Caused by a Novel Mutation in 11-β Hydroxysteroid Dehydrogenase Type 2 Enzyme: Its Genetics and Response to Therapy
.
Endocr Pract
.
2014
Sep
;
20
(
9
):
e151
6
.
[PubMed]
1530-891X
67.
Brand
E
,
Kato
N
,
Chatelain
N
,
Krozowski
ZS
,
Jeunemaitre
X
,
Corvol
P
, et al
Structural analysis and evaluation of the 11β−hydroxysteroid dehydrogenase type 2 (11β-HSD2) gene in human essential hypertension
.
J Hypertens
.
1998
;
16
:
1627
33
.
[PubMed]
0263-6352
68.
White
PC
,
Agarwal
AK
,
Li
A
,
Nikkila
H
,
Pratt
JH
,
Caulfield
M
, et al
Possible association but no linkage of the HSD11B2 gene encoding the kidney isozyme of 11beta-hydroxysteroid dehydrogenase to hypertension in Black people
.
Clin Endocrinol (Oxf)
.
2001
Aug
;
55
(
2
):
249
52
.
[PubMed]
0300-0664
69.
Agarwal
AK
,
Giacchetti
G
,
Lavery
G
,
Nikkila
H
,
Palermo
M
,
Ricketts
M
, et al
CA-Repeat polymorphism in intron 1 of HSD11B2 : effects on gene expression and salt sensitivity
.
Hypertension
.
2000
Aug
;
36
(
2
):
187
94
.
[PubMed]
0194-911X
70.
Williams
TA
,
Mulatero
P
,
Filigheddu
F
,
Troffa
C
,
Milan
A
,
Argiolas
G
, et al
Role of HSD11B2 polymorphisms in essential hypertension and the diuretic response to thiazides
.
Kidney Int
.
2005
Feb
;
67
(
2
):
631
7
.
[PubMed]
0085-2538
71.
Carvajal
CA
,
Romero
DG
,
Mosso
LM
,
González
AA
,
Campino
C
,
Montero
J
, et al
Biochemical and genetic characterization of 11 beta-hydroxysteroid dehydrogenase type 2 in low-renin essential hypertensives
.
J Hypertens
.
2005
Jan
;
23
(
1
):
71
7
.
[PubMed]
0263-6352
72.
Mune
T
,
Morita
H
,
Takada
N
,
Yamamoto
Y
,
Isomura
Y
,
Suwa
T
, et al
HSD11B2 CA-repeat and sodium balance
.
Hypertens Res
.
2013
Jul
;
36
(
7
):
614
9
.
[PubMed]
0916-9636
73.
Kotelevtsev
Y
,
Brown
RW
,
Fleming
S
,
Kenyon
C
,
Edwards
CR
,
Seckl
JR
, et al
Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2
.
J Clin Invest
.
1999
Mar
;
103
(
5
):
683
9
.
[PubMed]
0021-9738
74.
Craigie
E
,
Evans
LC
,
Mullins
JJ
,
Bailey
MA
.
Failure to downregulate the epithelial sodium channel causes salt sensitivity in Hsd11b2 heterozygote mice
.
Hypertension
.
2012
Sep
;
60
(
3
):
684
90
.
[PubMed]
0194-911X
75.
Ueda
K
,
Nishimoto
M
,
Hirohama
D
,
Ayuzawa
N
,
Kawarazaki
W
,
Watanabe
A
, et al
Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension
.
Hypertension
.
2017
Jul
;
70
(
1
):
111
8
.
[PubMed]
0194-911X
76.
Evans
LC
,
Ivy
JR
,
Wyrwoll
C
,
McNairn
JA
,
Menzies
RI
,
Christensen
TH
, et al
Conditional Deletion of Hsd11b2 in the Brain Causes Salt Appetite and Hypertension
.
Circulation
.
2016
Apr
;
133
(
14
):
1360
70
.
[PubMed]
0009-7322
77.
Seckl
JR
,
Holmes
MC
.
Mechanisms of disease: glucocorticoids, their placental metabolism and fetal ‘programming’ of adult pathophysiology
.
Nat Clin Pract Endocrinol Metab
.
2007
Jun
;
3
(
6
):
479
88
.
[PubMed]
1745-8366
78.
Wyrwoll
C
,
Keith
M
,
Noble
J
,
Stevenson
PL
,
Bombail
V
,
Crombie
S
, et al
Fetal brain 11beta-hydroxysteroid dehydrogenase type 2 selectively determines programming of adult depressive-like behaviors and cognitive function, but not anxiety behaviors in male mice. Psychoneuroendocrinology 2015 Sep;59:59-70. doi: . Epub;%
2015
May 18.:59-70.
79.
Cottrell
EC
,
Seckl
JR
,
Holmes
MC
,
Wyrwoll
CS
.
Foetal and placental 11β-HSD2: a hub for developmental programming
.
Acta Physiol (Oxf)
.
2014
Feb
;
210
(
2
):
288
95
.
[PubMed]
1748-1708
80.
Holmes
MC
,
Abrahamsen
CT
,
French
KL
,
Paterson
JM
,
Mullins
JJ
,
Seckl
JR
.
The mother or the fetus? 11beta-hydroxysteroid dehydrogenase type 2 null mice provide evidence for direct fetal programming of behavior by endogenous glucocorticoids
.
J Neurosci
.
2006
Apr
;
26
(
14
):
3840
4
.
[PubMed]
0270-6474
81.
Godfrey
KM
,
Barker
DJ
.
Fetal nutrition and adult disease
.
Am J Clin Nutr
.
2000
May
;
71
(
5
Suppl
):
1344S
52S
.
[PubMed]
0002-9165
82.
Newsome
CA
,
Shiell
AW
,
Fall
CH
,
Phillips
DI
,
Shier
R
,
Law
CM
.
Is birth weight related to later glucose and insulin metabolism?—A systematic review
.
Diabet Med
.
2003
May
;
20
(
5
):
339
48
.
[PubMed]
0742-3071
83.
Rogerson
FM
,
Kayes
KM
,
White
PC
.
Variation in placental type 2 11beta-hydroxysteroid dehydrogenase activity is not related to birth weight or placental weight
.
Mol Cell Endocrinol
.
1997
Apr
;
128
(
1-2
):
103
9
.
[PubMed]
0303-7207
84.
Räikkönen
K
,
Martikainen
S
,
Pesonen
AK
,
Lahti
J
,
Heinonen
K
,
Pyhälä
R
, et al
Maternal Licorice Consumption During Pregnancy and Pubertal, Cognitive, and Psychiatric Outcomes in Children
.
Am J Epidemiol
.
2017
Mar
;
185
(
5
):
317
28
.
[PubMed]
1476-6256
85.
White
PC
,
Rogoff
D
,
McMillan
DR
.
Physiological roles of 11 beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase
.
Curr Opin Pediatr
.
2008
Aug
;
20
(
4
):
453
7
.
[PubMed]
1040-8703
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.