PMID- 7792800
OWN - NLM
STAT- MEDLINE
DCOM- 19950724
LR  - 20190821
IS  - 0039-128X (Print)
IS  - 0039-128X (Linking)
VI  - 60
IP  - 1
DP  - 1995 Jan
TI  - Cortisol to cortisone: glucocorticoid to mineralocorticoid.
PG  - 143-6
AB  - 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), by converting cortisol and 
      corticosterone to hormonally inactive cortisone and 11-dehydrocorticosterone, 
      respectively, is an important pre-receptor signaling pathway for the renal 
      mineralocorticoid receptor (MR). This receptor has an equal affinity for the 
      glucocorticoids, cortisol and corticosterone, and for the mineralocorticoid, 
      aldosterone. In states of 11 beta-HSD deficiency such as the syndrome of apparent 
      mineralocorticoid excess (AME) and licorice ingestion, cortisol acts as a potent 
      mineralocorticoid. In addition to the established and cloned type I 11 beta-HSD, 
      a second 11 beta-HSD isoform has been reported in rabbit kidney and human 
      placenta. We have analyzed the kinetics of 11 beta-HSD activity in human kidney 
      and compared it with the expressed human type I 11 beta-HSD cDNA. Microsomes were 
      prepared from mid-gestational human fetal kidneys and incubated with various 
      concentrations of cortisol (0.0125-10 microM) and NAD or NADP. Kinetic analysis 
      revealed a high affinity (apparent Km 60 nM) isoform, the activity of which was 
      exclusively NAD-dependent. No convincing NADP-dependent activity was seen. 
      Similarly with cortisone as a substrate no 11-oxoreductase activity was evident. 
      In contrast, when type I human 11 beta-HSD was ligated into the expression vector 
      pcDNAI and transiently transfected into COS-I cells, low affinity (apparent Km 
      2.1 microM) NADP-dependent activity was seen. 11-Oxoreductase activity was also 
      observed. The cloned type I human 11 beta-HSD encodes an enzyme with both 
      low-affinity, NADP-dependent, dehydrogenase and 11-oxoreductase activities, but 
      this activity is absent in human fetal kidney (and probably adult 
      kidney).(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Stewart, P M
AU  - Stewart PM
AD  - Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, 
      United Kingdom.
FAU - Mason, J I
AU  - Mason JI
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Steroids
JT  - Steroids
JID - 0404536
RN  - 0 (Isoenzymes)
RN  - 0 (Mineralocorticoids)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - V27W9254FZ (Cortisone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Animals
MH  - Cortisone/*metabolism
MH  - Humans
MH  - Hydrocortisone/*metabolism
MH  - Hydroxysteroid Dehydrogenases/*metabolism
MH  - Isoenzymes/*metabolism
MH  - Kidney/embryology/metabolism
MH  - Microsomes, Liver/*enzymology
MH  - Mineralocorticoids/*metabolism
MH  - Rats
MH  - Tumor Cells, Cultured
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 0039-128X(94)00024-7 [pii]
AID - 10.1016/0039-128x(94)00024-7 [doi]
PST - ppublish
SO  - Steroids. 1995 Jan;60(1):143-6. doi: 10.1016/0039-128x(94)00024-7.