PMID- 18060684
OWN - NLM
STAT- MEDLINE
DCOM- 20080414
LR  - 20211020
IS  - 0303-7207 (Print)
IS  - 0303-7207 (Linking)
VI  - 281
IP  - 1-2
DP  - 2008 Jan 16
TI  - Pre-receptor regulation of the androgen receptor.
PG  - 1-8
AB  - The human androgen receptor (AR) is a ligand-activated nuclear transcription 
      factor and mediates the induction of genes involved in the development of the 
      male phenotype and male secondary sex characteristics, as well as the normal and 
      abnormal growth of the prostate. We have identified the pair of hydroxysteroid 
      dehydrogenases (HSDs) that regulate ligand access to the AR in human prostate. We 
      find that type 3 3alpha-HSD (aldo-keto reductase (AKR)1C2) catalyzes the NADPH 
      dependent reduction of the potent androgen 5alpha-dihydrotestosterone 
      (5alpha-DHT) to yield the inactive androgen 3alpha-androstanediol (3alpha-diol). 
      We also find that RoDH like 3alpha-HSD (RL-HSD) catalyzes the NAD(+) dependent 
      oxidation of 3alpha-diol to yield 5alpha-DHT. Together these enzymes are involved 
      in the pre-receptor regulation of androgen action. Inhibition of AKR1C2 would be 
      desirable in cases of androgen insufficiency and inhibition of RL-HSD might be 
      desirable in benign prostatic hyperplasia.
FAU - Penning, Trevor M
AU  - Penning TM
AD  - Center of Excellence in Environmental Toxicology, Department of Pharmacology, 
      University of Pennsylvania School of Medicine, Philadelphia 19104-6084, USA. 
      penning@pharm.med.upenn.edu
FAU - Jin, Yi
AU  - Jin Y
FAU - Rizner, Tea Lanisnik
AU  - Rizner TL
FAU - Bauman, David R
AU  - Bauman DR
LA  - eng
GR  - R01-CA90744/CA/NCI NIH HHS/United States
GR  - P30 ES013508/ES/NIEHS NIH HHS/United States
GR  - R01 DK047015/DK/NIDDK NIH HHS/United States
GR  - P30 ES013508-02/ES/NIEHS NIH HHS/United States
GR  - P30-ES013508/ES/NIEHS NIH HHS/United States
GR  - R01 DK047015-14A1/DK/NIDDK NIH HHS/United States
GR  - R01 CA090744/CA/NCI NIH HHS/United States
GR  - R01 CA090744-06A1/CA/NCI NIH HHS/United States
GR  - R01-DK-47015/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20071022
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Androgens)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Androgen)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.- (Aldo-Keto Reductases)
RN  - EC 1.1.1.21 (Aldehyde Reductase)
RN  - EC 1.1.1.357 (AKR1C2 protein, human)
SB  - IM
MH  - Alcohol Oxidoreductases/metabolism/physiology
MH  - Aldehyde Reductase
MH  - Aldo-Keto Reductases
MH  - Androgens/biosynthesis/metabolism
MH  - *Gene Expression Regulation
MH  - Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - Hydroxysteroid Dehydrogenases/genetics/metabolism/physiology
MH  - Ligands
MH  - Male
MH  - Models, Biological
MH  - Models, Molecular
MH  - Prostate/metabolism
MH  - Receptors, Androgen/*genetics
PMC - PMC2225387
MID - NIHMS37738
EDAT- 2007/12/07 09:00
MHDA- 2008/04/15 09:00
PMCR- 2009/01/15
CRDT- 2007/12/07 09:00
PHST- 2007/07/16 00:00 [received]
PHST- 2007/09/10 00:00 [revised]
PHST- 2007/10/15 00:00 [accepted]
PHST- 2007/12/07 09:00 [pubmed]
PHST- 2008/04/15 09:00 [medline]
PHST- 2007/12/07 09:00 [entrez]
PHST- 2009/01/15 00:00 [pmc-release]
AID - S0303-7207(07)00387-5 [pii]
AID - 10.1016/j.mce.2007.10.008 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2008 Jan 16;281(1-2):1-8. doi: 10.1016/j.mce.2007.10.008. 
      Epub 2007 Oct 22.