PMID- 11377978
OWN - NLM
STAT- MEDLINE
DCOM- 20010726
LR  - 20220408
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 77
IP  - 2-3
DP  - 2001 May
TI  - Modulation of the androgenic response by recombinant human 11-cis retinol 
      dehydrogenase.
PG  - 129-33
AB  - The 11-cis retinol dehydrogenase (11-cis-RoDH) enzyme catalyzes the oxidation of 
      cis-retinols to their respective retinals, a rate limiting step in the formation 
      of retinoic acids. Earlier, we have shown that the enzyme also exhibits an 
      oxidative 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) activity that can 
      convert 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) into 
      dihydrotestosterone (DHT), the most potent natural androgen. 11-cis-RoDH could 
      thus control the formation of two active hormones, namely 9-cis retinoic acid and 
      DHT. Therefore, depending upon the substrate availability in the various tissues, 
      this enzyme could provide different metabolites for specific cell functions. To 
      further investigate the role of 11-cis-RoDH in the formation of DHT from 
      3alpha-diol, we stably expressed the enzyme in the human embryonic kidney cell 
      line 293 (HEK-293). The transformation of 3alpha-diol by these cells was 
      evaluated by assays using both microsomal fractions and intact cultured cells 
      stably expressing 11-cis-RoDH. The results show that in the intact cells 
      11-cis-RoDH only catalyzes the oxidation of 3alpha-diol into DHT whereas the 
      microsomal fraction catalyzes both the oxidation and the reduction reactions 
      depending upon whether NAD(+) or NADH is added. Furthermore, we examined the 
      ability of 11-cis-RoDH, through the production from 3alpha-diol of the active 
      androgen DHT, to activate the androgen-responsive promoter of the 
      prostate-specific antigen (PSA) gene. The co-transfection of the pCMV expression 
      vector containing 11-cis-RoDH (pCMV-11-cisRoDH), a luciferase reporter gene 
      driven by a PSA promoter (pCMV-PSA-Luc) and an androgen receptor (pCMV-hAR) 
      showed that, in the presence of 3alpha-diol, the expression of the PSA promoter 
      is increased by five to six-fold. Moreover, this stimulatory effect is inhibited 
      by hydroxyflutamide, a well-known antiandrogen. These results suggest that 
      11-cis-RoDH could be involved in a non-classical pathway of androgen formation 
      and might play a role in the modulation of the androgenic response in some 
      peripheral tissues.
FAU - Huang, X F
AU  - Huang XF
AD  - Oncology and Molecular Endocrinology Research Center, Laval University Hospital 
      Center (CHUL) and Laval University, 2705 Laurier Boulevard, Sainte-Foy, Quebec, 
      Canada G1V 4G2.
FAU - Luu-The, V
AU  - Luu-The V
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 (Recombinant Proteins)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.105 (retinol dehydrogenase)
SB  - IM
MH  - Alcohol Oxidoreductases/genetics/metabolism/*pharmacology
MH  - Androgens/*physiology
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Genes, Reporter
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Recombinant Proteins/genetics/metabolism/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
EDAT- 2001/05/30 10:00
MHDA- 2001/07/28 10:01
CRDT- 2001/05/30 10:00
PHST- 2001/05/30 10:00 [pubmed]
PHST- 2001/07/28 10:01 [medline]
PHST- 2001/05/30 10:00 [entrez]
AID - S0960-0760(01)00038-3 [pii]
AID - 10.1016/s0960-0760(01)00038-3 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2001 May;77(2-3):129-33. doi: 
      10.1016/s0960-0760(01)00038-3.