PMID- 8031722
OWN - NLM
STAT- MEDLINE
DCOM- 19940816
LR  - 20190830
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 49
IP  - 2-3
DP  - 1994 Jun
TI  - Evidence for distinct isoforms of 11 beta-hydroxysteroid dehydrogenase in the 
      ovine liver and kidney.
PG  - 245-50
AB  - We have previously identified a unique 11 beta-hydroxysteroid dehydrogenase (11 
      beta-HSD) transcript in the ovine kidney. To examine whether this is indicative 
      of a distinct isoform with respect to enzymatic activity, we studied and compared 
      the characteristics of 11 beta-HSD activity in the ovine liver and kidney. 11 
      beta-HSD activity was determined by a radiometric conversion assay using cortisol 
      and cortisone as physiological substrates. Although in both liver and kidney, the 
      enzyme was localized by subcellular fractionation in the microsomes, the renal 11 
      beta-HSD displayed distinct characteristics in that it expressed only 
      dehydrogenase activity and utilized almost exclusively NAD as cofactor (the 
      respective activity in the presence of NAD and NADP was 190 +/- 26 and 12 +/- 2 
      pmol/min/mg protein). By contrast, the liver enzyme contained both dehydrogenase 
      and reductase activities, and displayed preference for NADP and NADPH, 
      respectively. Furthermore, with cortisol as substrate, the kidney 11 beta-HSD had 
      a Km of 68 +/- 7 nM which was over 100 times lower than the hepatic enzyme (8 +/- 
      1 microM). In addition, the renal 11 beta-HSD activity was inhibited in a 
      dose-dependent fashion by both carbenoxolone, a potent inhibitor of 11 beta-HSD, 
      and the end product cortisone, whereas the liver enzyme showed little inhibition 
      by either substance. In summary, these results provide strong evidence for the 
      existence of distinct isoforms of 11 beta-HSD with respect to enzymatic activity 
      in the ovine liver and kidney. In addition, the characteristics of the kidney 
      enzyme closely resemble those of that described previously in the rabbit renal 
      aldosterone target cells, and thus further demonstrating the presence of an 
      isoform of 11 beta-HSD distinct from the NADP-dependent enzyme purified and 
      cloned from the rat liver.
FAU - Yang, K
AU  - Yang K
AD  - Lawson Research Institute, Department of Obstetrics and Gynecology, University of 
      Western Ontario, St Joseph's Health Centre, London, Canada.
FAU - Yu, M
AU  - Yu M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Isoenzymes)
RN  - 0U46U6E8UK (NAD)
RN  - 53-59-8 (NADP)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - MM6384NG73 (Carbenoxolone)
RN  - V27W9254FZ (Cortisone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Animals
MH  - Carbenoxolone/pharmacology
MH  - Cell Fractionation
MH  - Cortisone/metabolism
MH  - Female
MH  - Hydrocortisone/metabolism
MH  - Hydroxysteroid Dehydrogenases/antagonists & inhibitors/*metabolism
MH  - Isoenzymes/*metabolism
MH  - Kidney/*enzymology/ultrastructure
MH  - Kinetics
MH  - Liver/*enzymology
MH  - Microsomes/enzymology
MH  - Microsomes, Liver/enzymology
MH  - NAD/pharmacology
MH  - NADP/pharmacology
MH  - Pregnancy
MH  - Sheep
EDAT- 1994/06/01 00:00
MHDA- 1994/06/01 00:01
CRDT- 1994/06/01 00:00
PHST- 1994/06/01 00:00 [pubmed]
PHST- 1994/06/01 00:01 [medline]
PHST- 1994/06/01 00:00 [entrez]
AID - 0960-0760(94)90016-7 [pii]
AID - 10.1016/0960-0760(94)90016-7 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1994 Jun;49(2-3):245-50. doi: 
      10.1016/0960-0760(94)90016-7.