PMID- 8732505
OWN - NLM
STAT- MEDLINE
DCOM- 19961112
LR  - 20071114
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 28
IP  - 4
DP  - 1996 Apr
TI  - High affinity NAD(+)-dependent 11 beta-hydroxysteroid dehydrogenase in the human 
      heart.
PG  - 781-7
AB  - Receptor-ligand binding is an essential component of mineralocorticoid (MC) 
      activity in target tissues. Detection of type 1 mineralocorticoid receptors (MR) 
      in cardiac tissue is therefore suggestive that, like kidney, the heart is MC 
      responsive. The presence of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) 
      within MC responsive tissue is essential to prevent saturation of MR by 
      glucocorticoids. Using both high-performance liquid chromatography (HPLC) and 
      thin layer chromatography (TLC), we have found that a high-affinity species of 11 
      beta-HSD predominates within human heart. Although two 11 beta-HSD isoforms were 
      detected in human cardiac tissues, the activity of high-affinity (type 2) 11 
      beta-HSD was found to be at least twice that of low affinity (type 1) 11 
      beta-HSD. Human cardiac type 2 11 beta-HSD possesses characteristics identical to 
      the high-affinity enzyme of distal renal tubules; 11 beta-dehydrogenation of 
      corticosterone or cortisol to their 11-keto metabolites is NAD(+)-dependent and, 
      with corticosterone as substrate, the enzyme has a nanomolar Km (15.1 nM as 
      determined by Lineweaver-Burke analysis). Furthermore, its activity is 
      unidirectional; corticosterone and cortisol are 11 beta-dehydrogenated to 
      inactive 11-keto metabolites, whereas 11-oxoreductase activity (conversion of 
      11-dehydrocorticosterone and cortisone to corticosterone and cortisol, 
      respectively) is absent. RT/PCR analysis, using primers complementary to the 
      human renal type 2 11 beta-HSD sequence, demonstrated that the high-affinity 
      species of 11 beta-HSD expressed in human heart is indeed the same enzyme as that 
      produced in the kidney. These findings strongly suggest that, as is the case in 
      the distal portion of the nephron, type 2 11 beta-HSD plays an important role in 
      the human heart to promote glucocorticoid metabolism and to confer MC specificity 
      upon MR.
FAU - Slight, S H
AU  - Slight SH
AD  - Department of Internal Medicine, University of Missouri Health Sciences Center, 
      Columbia, USA.
FAU - Ganjam, V K
AU  - Ganjam VK
FAU - Gomez-Sanchez, C E
AU  - Gomez-Sanchez CE
FAU - Zhou, M Y
AU  - Zhou MY
FAU - Weber, K T
AU  - Weber KT
LA  - eng
GR  - R01-HL-31701/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Steroid)
RN  - EC 1.6.99.1 (NADPH Dehydrogenase)
SB  - IM
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid
MH  - Chromatography, Thin Layer
MH  - Glucocorticoids/metabolism
MH  - Heart Transplantation
MH  - Humans
MH  - Molecular Sequence Data
MH  - Myocardium/cytology/*enzymology
MH  - NADPH Dehydrogenase/isolation & purification/*metabolism
MH  - Polymerase Chain Reaction
MH  - Receptors, Steroid/metabolism
EDAT- 1996/04/01 00:00
MHDA- 1996/04/01 00:01
CRDT- 1996/04/01 00:00
PHST- 1996/04/01 00:00 [pubmed]
PHST- 1996/04/01 00:01 [medline]
PHST- 1996/04/01 00:00 [entrez]
AID - S0022-2828(96)90072-3 [pii]
AID - 10.1006/jmcc.1996.0072 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 1996 Apr;28(4):781-7. doi: 10.1006/jmcc.1996.0072.