PMID- 24055403
OWN - NLM
STAT- MEDLINE
DCOM- 20150223
LR  - 20220321
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 254
DP  - 2013 Dec 19
TI  - The role of androgen receptor in transcriptional modulation of cannabinoid 
      receptor type 1 gene in rat trigeminal ganglia.
PG  - 395-403
LID - S0306-4522(13)00785-9 [pii]
LID - 10.1016/j.neuroscience.2013.09.014 [doi]
AB  - We have previously shown that anti-hyperalgesic effects of cannabinoid agonists 
      under inflammatory condition are much greater in male than female, and that 
      inflammatory cytokines upregulate cannabinoid receptor type 1 (CB1) expression in 
      male, but not female, trigeminal ganglia (TG) in a testosterone-dependent manner. 
      In this study, we investigated the mechanisms underlying the 
      testosterone-mediated regulation of peripheral CB1 expression. We hypothesized 
      that testosterone upregulates CB1 through transcriptional modulation by androgen 
      receptor (AR). Interleukin-1 beta (IL-1beta), a pro-inflammatory cytokine, 
      upregulated CB1 mRNA expression in TG of male rats. The cytokine-induced 
      upregulation was prevented by the pretreatment with flutamide, a specific 
      antagonist for AR, but not by ICI 182,780, a specific antagonist for estrogen 
      receptor, suggesting that the effects of testosterone are not mediated by 
      estradiol, a testosterone metabolite. The expression levels of AR and IL-1beta 
      receptors were comparable between male and female TG, suggesting that the male 
      specific IL-1beta effects on CB1 upregulation occurs downstream to these receptors. 
      The chromatin immunoprecipitation assay showed AR binding to the CB1 promoter in 
      the rat TG. Furthermore, luciferase reporter assay revealed that AR activated the 
      CB1 gene in response to testosterone or dihydrotestosterone treatment. These 
      experiments provided compelling evidence that testosterone regulates CB1 gene 
      transcription in TG through AR following cytokine stimulation. These results 
      should provide mechanistic bases for understanding cytokine-hormone-neuron 
      interactions in peripheral cannabinoid systems, and have important clinical 
      implications for pain patients in whom testosterone level is naturally low, 
      gradually declining or pharmacologically compromised.
CI  - Copyright (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Lee, K S
AU  - Lee KS
AD  - University of Maryland Dental School, Department of Neural and Pain Sciences, 
      Program in Neuroscience, Baltimore, MD 21201, USA.
FAU - Asgar, J
AU  - Asgar J
FAU - Zhang, Y
AU  - Zhang Y
FAU - Chung, M-K
AU  - Chung MK
FAU - Ro, J Y
AU  - Ro JY
LA  - eng
GR  - R01 DE019448/DE/NIDCR NIH HHS/United States
GR  - R01DE19448/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130917
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Female
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Protein Binding/physiology
MH  - Rats
MH  - Receptor, Cannabinoid, CB1/*biosynthesis/genetics
MH  - Receptors, Androgen/*physiology
MH  - Transcription, Genetic/*physiology
MH  - Trigeminal Ganglion/*metabolism
PMC - PMC3870904
MID - NIHMS525991
OTO - NOTNLM
OT  - ANOVA
OT  - AR
OT  - CB1
OT  - ChIP
OT  - Cnr1
OT  - EDTA
OT  - ER
OT  - IL-1R
OT  - IL-1beta
OT  - PBS
OT  - RIPA
OT  - RT-PCR
OT  - TG
OT  - analysis of variance
OT  - androgen receptor
OT  - cannabinoid receptor 1
OT  - cannabinoid receptor type 1
OT  - chromatin immunoprecipitation
OT  - cytokines
OT  - estrogen receptor
OT  - ethylenediaminetetraacetic acid
OT  - inflammation
OT  - interleukin-1 beta
OT  - interleukin-1 beta receptor
OT  - phosphate-buffered saline
OT  - radio-immunoprecipitation assay
OT  - rat
OT  - reverse transcription polymerase chain reaction
OT  - sensory neurons
OT  - testosterone
OT  - trigeminal ganglia
COIS- CONFLICT OF INTEREST There are no conflicts of interest associated with the 
      present study.
EDAT- 2013/09/24 06:00
MHDA- 2015/02/24 06:00
PMCR- 2014/12/19
CRDT- 2013/09/24 06:00
PHST- 2013/05/29 00:00 [received]
PHST- 2013/09/04 00:00 [revised]
PHST- 2013/09/05 00:00 [accepted]
PHST- 2013/09/24 06:00 [entrez]
PHST- 2013/09/24 06:00 [pubmed]
PHST- 2015/02/24 06:00 [medline]
PHST- 2014/12/19 00:00 [pmc-release]
AID - S0306-4522(13)00785-9 [pii]
AID - 10.1016/j.neuroscience.2013.09.014 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Dec 19;254:395-403. doi: 10.1016/j.neuroscience.2013.09.014. 
      Epub 2013 Sep 17.