PMID- 8031714
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  - 11 beta-Hydroxysteroid dehydrogenase and tissue specificity of androgen action in 
      human prostate cancer cell LNCaP.
PG  - 173-81
AB  - Incubation of whole LNCaP cells in suspension with tritium labeled cortisol 
      revealed two major and one minor radioactive product. Of the major products, one 
      migrated with an Rf value identical to cortisol (Kendall's compound "F"), and the 
      second migrated with an Rf value similar to nonradioactive cortisone (Kendall's 
      compound "E"); the third minor product comigrated with 21-acetylated cortisol. 
      The conversion of cortisol to cortisone was linear with respect to cell number, 
      and conversion reached a plateau after 120 min of incubation at 37 degrees C. One 
      half of the cortisol was converted to cortisone within 2 h of incubation at 37 
      degrees C. This conversion was nicotine amide dinucleotide (NAD) dependent. Low 
      levels of transcription activation by cortisol were documented in LNCaP cells 
      transfected with glucocorticoid and androgen responsive mouse mammary tumor 
      virus-bacterial chloramphenicol acetyltransferase chimeric gene (MMTV-CAT). 
      Hormone binding assay and transactivation analysis revealed the presence of a 
      functional mineralocorticoid receptor in LNCaP cells. Treatment of transfectants 
      with F in the presence of carbenoxolone, a potent inhibitor of 11 
      beta-hydroxysteroid dehydrogenase (11 beta-HSD), resulted in a two orders of 
      magnitude increase in measurable CAT activity. The addition of the reduced form 
      of nicotine amide dinucleotide (NADH) in the presence of 10(-7) M E stimulated 
      measurable CAT activity in LNCaP cells. In conferring aldosterone specificity in 
      mineralocorticoid target tissues, 11 beta-HSD may have an important role as "gate 
      keeper" in allowing a specific androgen response in hormone responsive LNCaP 
      prostate cancer cells.
FAU - Page, N
AU  - Page N
AD  - M.R.C. Group in Molecular Endocrinology, Quebec, Canada.
FAU - Warriar, N
AU  - Warriar N
FAU - Govindan, M V
AU  - Govindan MV
LA  - eng
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 (Androgens)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 0U46U6E8UK (NAD)
RN  - 10028-17-8 (Tritium)
RN  - 4964P6T9RB (Aldosterone)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - MM6384NG73 (Carbenoxolone)
RN  - V27W9254FZ (Cortisone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Acetylation
MH  - Aldosterone/metabolism
MH  - Androgens/*pharmacology
MH  - Carbenoxolone/pharmacology
MH  - Chloramphenicol O-Acetyltransferase/genetics/metabolism
MH  - Cortisone/metabolism
MH  - Humans
MH  - Hydrocortisone/metabolism/pharmacology
MH  - Hydroxysteroid Dehydrogenases/antagonists & inhibitors/*metabolism
MH  - Male
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - NAD/pharmacology
MH  - Prostatic Neoplasms/*enzymology/metabolism
MH  - Receptors, Mineralocorticoid/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Transfection
MH  - Tritium
MH  - Tumor Cells, Cultured
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)90008-6 [pii]
AID - 10.1016/0960-0760(94)90008-6 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1994 Jun;49(2-3):173-81. doi: 
      10.1016/0960-0760(94)90008-6.