PMID- 15276623
OWN - NLM
STAT- MEDLINE
DCOM- 20040923
LR  - 20131121
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 91
IP  - 3
DP  - 2004 Jul
TI  - Partitioning of 5alpha-dihydrotestosterone and 5alpha-androstane-3alpha, 
      17beta-diol activated pathways for stimulating human prostate cancer LNCaP cell 
      proliferation.
PG  - 157-70
AB  - The growth and development of the prostate gland are regulated by androgens. 
      Despite our understanding of molecular actions of 5alpha-dihydrotestosterone 
      (5alpha-DHT) in the prostate through the trans-activation of the androgen 
      receptor (AR), comprehensive analysis of androgen responsive genes (ARGs) has 
      just been started. Moreover, expression changes induced by the androgen effects 
      of 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), a metabolite of 5alpha-DHT 
      through the action of 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs), remain 
      undefined. We demonstrated that both 5alpha-DHT and 3alpha-diol stimulated 
      similar levels of androgen sensitive human prostate cancer LNCaP cell 
      proliferation. However, consistent with the fact that 3alpha-diol has low 
      affinity toward the AR, 3alpha-diol did not elicit the same levels of AR 
      trans-activation activity as that of 5alpha-DHT. Since LNCaP cells respond to 
      androgen stimulation by transcriptionally activating the AR downstream genes, 
      gene expression patterns between 0 and 48 h following 3alpha-diol and 5alpha-DHT 
      stimulation were analyzed using cDNA-based membrane arrays to define the temporal 
      regulation of ARGs. Array analysis identified 217 and 219 androgen-modulated 
      genes in at least one time point following 3alpha-diol and 5alpha-DHTstimulation, 
      respectively, including key regulators of cell proliferation. Only a subset of 
      these genes (143) was regulated by both androgens. These data suggest that 
      3alpha-diol exerts androgenic effects independent of the action of 5alpha-DHT in 
      steroid target tissues. Accordingly, 3alpha-diol might activate cell 
      proliferation cascades independent of AR pathway in the prostate.
CI  - Copyright 2004 Elsevier Ltd.
FAU - Nunlist, Eva H
AU  - Nunlist EH
AD  - Department of Urology, University of Oklahoma Health Sciences Center, 920 Stanton 
      L. Young Blvd., WP3150, Oklahoma City, OK 73104, USA.
FAU - Dozmorov, Igor
AU  - Dozmorov I
FAU - Tang, Yuhong
AU  - Tang Y
FAU - Cowan, Rick
AU  - Cowan R
FAU - Centola, Michael
AU  - Centola M
FAU - Lin, Hsueh-Kung
AU  - Lin HK
LA  - eng
GR  - DK54925/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Receptors, Androgen)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 25126-76-5 (Androstane-3,17-diol)
SB  - IM
MH  - Androstane-3,17-diol/*physiology
MH  - Cell Division/*drug effects
MH  - Cell Line, Tumor
MH  - Dihydrotestosterone/*metabolism
MH  - Gene Expression Profiling
MH  - Humans
MH  - Male
MH  - Oligonucleotide Array Sequence Analysis
MH  - Prostatic Neoplasms/genetics/*pathology
MH  - Receptors, Androgen/genetics
EDAT- 2004/07/28 05:00
MHDA- 2004/09/24 05:00
CRDT- 2004/07/28 05:00
PHST- 2003/09/03 00:00 [received]
PHST- 2004/02/24 00:00 [accepted]
PHST- 2004/07/28 05:00 [pubmed]
PHST- 2004/09/24 05:00 [medline]
PHST- 2004/07/28 05:00 [entrez]
AID - S0960076004002237 [pii]
AID - 10.1016/j.jsbmb.2004.02.008 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2004 Jul;91(3):157-70. doi: 
      10.1016/j.jsbmb.2004.02.008.