PMID- 8979285
OWN - NLM
STAT- MEDLINE
DCOM- 19970318
LR  - 20190914
IS  - 0031-3998 (Print)
IS  - 0031-3998 (Linking)
VI  - 41
IP  - 1
DP  - 1997 Jan
TI  - 11 beta-Hydroxysteroid dehydrogenase and its role in the syndrome of apparent 
      mineralocorticoid excess.
PG  - 25-9
AB  - Aldosterone, the most important mineralocorticoid, regulates electrolyte 
      excretion and intravascular volume mainly through its effects on renal distal 
      tubules and cortical collecting ducts, where it acts to increase sodium 
      resorption from and potassium excretion into the urine. Excess secretion of 
      aldosterone or other mineralocorticoids, or abnormal sensitivity to 
      mineralocorticoids, may results in hypokalemia, suppressed plasma renin activity, 
      and hypertension. The syndrome of apparent mineralocorticoid excess (AME) is an 
      inherited form of hypertension in which 11 beta-hydroxysteroid dehydrogenase (11 
      beta-HSD) is defective. This enzyme converts cortisol to its inactive metabolite, 
      cortisone. Because mineralocorticoid receptors themselves have similar affinities 
      for cortisol and aldosterone, it is hypothesized that the deficiency allows these 
      receptors to be occupied by cortisol, which normally circulates at levels far 
      higher than those of aldosterone. We cloned cDNA and genes encoding two isozymes 
      of 11 beta-HSD. The liver (L) or type 1 isozyme has relatively low affinity for 
      steroids, is expressed at high levels in the liver but poorly in the kidney, and 
      is not defective in AME. The kidney (K) or type 2 isozyme has high steroid 
      affinity and is expressed at high levels in the kidney and placenta. Mutations in 
      the gene for the latter isozyme have been detected in all kindreds with AME. 
      Moreover, the in vitro enzymatic activity conferred by each mutation is strongly 
      correlated with the ratio of cortisol to cortisone metabolites in the urine 
      [tetrahydrocortisone (THF) +allo-THF]/THE. This suggests that the biochemical 
      phenotype of AME is largely determined by genotype.
FAU - White, P C
AU  - White PC
AD  - Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 
      75235-9063, USA.
FAU - Mune, T
AU  - Mune T
FAU - Rogerson, F M
AU  - Rogerson FM
FAU - Kayes, K M
AU  - Kayes KM
FAU - Agarwal, A K
AU  - Agarwal AK
LA  - eng
GR  - DK42169/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - 0 (DNA, Complementary)
RN  - 0 (Isoenzymes)
RN  - 0 (Mineralocorticoids)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Cloning, Molecular
MH  - DNA, Complementary/metabolism
MH  - Humans
MH  - Hydroxysteroid Dehydrogenases/deficiency/genetics/*metabolism
MH  - Hypertension/etiology/physiopathology
MH  - Isoenzymes/genetics
MH  - Mineralocorticoids/*metabolism
MH  - Mutation
MH  - Syndrome
RF  - 37
EDAT- 1997/01/01 00:00
MHDA- 1997/01/01 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1997/01/01 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
AID - 10.1203/00006450-199701000-00004 [doi]
PST - ppublish
SO  - Pediatr Res. 1997 Jan;41(1):25-9. doi: 10.1203/00006450-199701000-00004.