PMID- 9683905
OWN - NLM
STAT- MEDLINE
DCOM- 19980826
LR  - 20190512
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 38
IP  - 1
DP  - 1998 Apr
TI  - The role of 11 beta-hydroxysteroid dehydrogenase in the pathogenesis of 
      hypertension.
PG  - 16-24
AB  - The two 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isozymes catalyze the 
      interconversion of cortisol and cortisone. Type 1 11 beta-HSD (11 beta-HSD1) has 
      bidirectional activity, while type 2 11 beta-HSD (11 beta-HSD2) mainly converts 
      cortisol into cortisone. Of these two hormones only cortisol has affinity to 
      mineralocorticoid receptors (MRs) and thus induces mineralocorticoid effects. A 
      normal activity of 11 beta-HSD2 is crucial for prevention of mineralocorticoid 
      activity of cortisol. Absent or decreased 11 beta-HSD2 activity results in 
      cortisol-mediated hypermineralocorticoid hypertension. In several hypertensive 
      syndromes a decreased 11 beta-HSD2 activity has been described as the 
      pathogenetic mechanism of the increased blood pressure. In the apparent mineral 
      corticoid excess (AME) syndrome type 1, absence of 11 beta-HSD2 activity is 
      caused by mutations in the gene coding for 11 beta-HSD2. In licorice-induced 
      hypertension glycyrrhetinic acid, the active substituent of licorice, inhibits 11 
      beta-HSD2 resulting in an acquired hypermineralocorticoid state. 11 beta-HSD2 
      activity is not decreased in glucocorticoid hypertension (Cushing's syndrome). In 
      essential hypertension some evidence for decreased systemic and skin activity of 
      11 beta-HSD1 and/or 11 beta-HSD2 has been found, while renal activity of both 
      isozymes appears to be normal. 11 beta-HSD2 activity is also present in 
      cardiovascular myocytes of humans and dogs, and inhibition of 11 beta-HSD 
      potentiates the vascular response to catecholamines. Although MRs in the central 
      nervous system have been incriminated in the pathogenesis of mineralocorticoid 
      hypertension, a pathophysiological role for 11 beta-HSD2 has not yet been 
      described. Finally, in the placenta 11 beta-HSD2 reduces fetal exposure to 
      maternal glucocorticoids and a decreased activity of this isozyme may result in 
      low birth weight and increased risk of high blood pressure at adult age.
FAU - van Uum, S H
AU  - van Uum SH
AD  - Department of Medicine, St. Radboud University Hospital, University of Nijmegen, 
      Netherlands. s.vanuum@aig.azn.nl
FAU - Hermus, A R
AU  - Hermus AR
FAU - Smits, P
AU  - Smits P
FAU - Thien, T
AU  - Thien T
FAU - Lenders, J W
AU  - Lenders JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Isoenzymes)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - P540XA09DR (Glycyrrhetinic Acid)
RN  - V27W9254FZ (Cortisone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Cortisone/metabolism
MH  - Glycyrrhetinic Acid/metabolism
MH  - Humans
MH  - Hydrocortisone/metabolism
MH  - Hydroxysteroid Dehydrogenases/*physiology
MH  - Hypertension/*enzymology
MH  - Isoenzymes/physiology
MH  - Receptors, Mineralocorticoid/metabolism
RF  - 107
EDAT- 1998/07/31 00:00
MHDA- 1998/07/31 00:01
CRDT- 1998/07/31 00:00
PHST- 1998/07/31 00:00 [pubmed]
PHST- 1998/07/31 00:01 [medline]
PHST- 1998/07/31 00:00 [entrez]
AID - S0008-6363(97)00299-X [pii]
AID - 10.1016/s0008-6363(97)00299-x [doi]
PST - ppublish
SO  - Cardiovasc Res. 1998 Apr;38(1):16-24. doi: 10.1016/s0008-6363(97)00299-x.