PMID- 1954223
OWN - NLM
STAT- MEDLINE
DCOM- 19911231
LR  - 20190609
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1075
IP  - 3
DP  - 1991 Oct 31
TI  - Inhibition of rat renal 11 beta-hydroxysteroid dehydrogenase by steroidal 
      compounds and triterpenoids; structure/function relationship.
PG  - 206-12
AB  - Various compounds with steroidal structure were tested for inhibitory effects on 
      enzymatic activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) from rat 
      renal microsomes. Most substances exerting inhibitory potency on both the 
      oxidative as well as the reductive activity can be classified into two main 
      groups: pentacyclic triterpenoids of the oleane type and steroidal detergents of 
      the CHAPS-series. Inhibition is competitive, as was shown for one compound of 
      each group. The IC50 values of the various inhibitors range over five orders of 
      magnitude. In all cases, oxidative activity was inhibited more effectively than 
      reductive activity. An attempt has been made to correlate structural properties 
      and inhibitory potency. In brief, inhibition seems to be enhanced by a C11-oxygen 
      function, which is present in all endogenous glucocorticosteroids and a C7-OH 
      function. Inhibition is reduced by a large and polar substituent at C3 in the 
      A-ring. A large D-ring substituent, such as a bisgluconamidopropyl side chain or 
      even an additional E-ring, does not prevent binding to the enzyme, although 
      inhibition seems to be influenced by its steric conformation. The cardiac 
      glycosides and steroidal antibiotics tested exert no inhibitory effect on 11 
      beta-HSD. Cholesterol and pentacyclic triterpenoids of the lupane type exhibit a 
      very poor inhibition, probably caused by the localization of planar structures in 
      the ring systems, which differs from that of the effective oleane type 
      inhibitors.
FAU - Buhler, H
AU  - Buhler H
AD  - Institut fur Klinische Physiologie, Klinikum Steglitz, Freie Universitat Berlin, 
      F.R.G.
FAU - Perschel, F H
AU  - Perschel FH
FAU - Hierholzer, K
AU  - Hierholzer K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Steroids)
RN  - 0 (Triterpenes)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Animals
MH  - Hydroxysteroid Dehydrogenases/*antagonists & inhibitors
MH  - In Vitro Techniques
MH  - Kidney/*enzymology
MH  - Male
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Steroids/*pharmacology
MH  - Structure-Activity Relationship
MH  - Triterpenes/*pharmacology
EDAT- 1991/10/31 00:00
MHDA- 1991/10/31 00:01
CRDT- 1991/10/31 00:00
PHST- 1991/10/31 00:00 [pubmed]
PHST- 1991/10/31 00:01 [medline]
PHST- 1991/10/31 00:00 [entrez]
AID - 0304-4165(91)90268-L [pii]
AID - 10.1016/0304-4165(91)90268-l [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1991 Oct 31;1075(3):206-12. doi: 
      10.1016/0304-4165(91)90268-l.