PMID- 9496245
OWN - NLM
STAT- MEDLINE
DCOM- 19980316
LR  - 20190709
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 156
IP  - 1
DP  - 1998 Jan
TI  - Regulation of 11 beta-hydroxysteroid dehydrogenase type 1 in primary cultures of 
      rat and human hepatocytes.
PG  - 159-68
AB  - Two isozymes of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) are 
      responsible for the interconversion of the active glucocorticoid, cortisol in 
      man, (corticosterone in the rodent), to the inactive 11-keto metabolite, 
      cortisone (11-dehydrocorticosterone). We have examined the regulation of type 1 
      11 beta-HSD (11 beta-HSD1) using primary cultures of rat and human hepatocytes, 
      both of which express only 11 beta-HSD1. Only 11 oxo-reductase activity could be 
      demonstrated in cultured hepatocytes (apparent Km for cortisone 382 +/- 43 nM in 
      human hepatocytes, apparent Km for 11-dehydrocorticosterone 14.6 +/- 1.5 microM 
      in rat hepatocytes). There exists a marked discrepancy between 11 beta-HSD 
      oxo-reductase activity and 11 beta-HSD1 mRNA levels in cultured human hepatocytes 
      and human liver. Thus oxo-reductase specific activity is much higher in the 
      cultured hepatocytes (7.2 +/- 0.01 nmoles cortisol/mg/h vs 0.89 +/- 0.06 for 
      whole liver homogenates) whilst the converse is true for steady state 11 
      beta-HSD1 mRNA levels (0.78 +/- 0.02 vs 1.94 +/- 0.07 in whole liver, 11 
      beta-HSD1/18S expressed as arbitrary units). Carbenoxolone has a significant 
      inhibitory effect on 11 oxo-reductase activity in both rat and human hepatocytes. 
      However, there is clear species-specific regulation of 11 oxo-reductase activity 
      by thyroid hormone (tri-iodothyronine (T3)), which increases 11 oxo-reductase 
      activity in rat hepatocytes but has no effect on activity in human hepatocytes, 
      and progesterone which inhibits activity in human hepatocytes, but has no effect 
      on activity in rat hepatocytes. Neither T3 nor progesterone altered 11 beta-HSD1 
      mRNA levels. A series of growth factors (hepatocyte growth factor, epidermal 
      growth factor, basic fibroblast growth factor, transforming growth factor beta 1) 
      were without effect on 11 oxo-reductase activity in cultured rat hepatocytes. In 
      contrast to homogenates of human liver, cultured hepatocytes express only 11 
      beta-HSD oxo-reductase activity. This is inhibited by carbenoxolone and shows 
      species-specific regulation by T3 and progesterone. Growth factors do not appear 
      to regulate activity or expression of 11 beta-HSD1. The discrepant enzyme 
      activity data and 11 beta-HSD1 mRNA expression in hepatocytes and whole liver 
      could reflect unstable 11 beta-HSD1 oxo-reductase activity or, alternatively, an 
      additional 11 beta-HSD oxo-reductase isoform in cultured hepatocytes.
FAU - Ricketts, M L
AU  - Ricketts ML
AD  - Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, 
      Edgbaston, UK.
FAU - Shoesmith, K J
AU  - Shoesmith KJ
FAU - Hewison, M
AU  - Hewison M
FAU - Strain, A
AU  - Strain A
FAU - Eggo, M C
AU  - Eggo MC
FAU - Stewart, P M
AU  - Stewart PM
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - FO4V44A3G3 (11-dehydrocorticosterone)
RN  - MM6384NG73 (Carbenoxolone)
RN  - V27W9254FZ (Cortisone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Blotting, Northern
MH  - Carbenoxolone/pharmacology
MH  - Cells, Cultured
MH  - Child
MH  - Corticosterone/analogs & derivatives/metabolism
MH  - Cortisone/metabolism
MH  - Humans
MH  - Hydroxysteroid Dehydrogenases/genetics/*metabolism
MH  - Isoenzymes/*metabolism
MH  - Liver/cytology/drug effects/*enzymology
MH  - Male
MH  - Middle Aged
MH  - Progesterone/pharmacology
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Species Specificity
MH  - Triiodothyronine/pharmacology
EDAT- 1998/03/13 00:00
MHDA- 1998/03/13 00:01
CRDT- 1998/03/13 00:00
PHST- 1998/03/13 00:00 [pubmed]
PHST- 1998/03/13 00:01 [medline]
PHST- 1998/03/13 00:00 [entrez]
AID - 10.1677/joe.0.1560159 [doi]
PST - ppublish
SO  - J Endocrinol. 1998 Jan;156(1):159-68. doi: 10.1677/joe.0.1560159.