PMID- 27320211
OWN - NLM
STAT- MEDLINE
DCOM- 20170711
LR  - 20220321
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 331
DP  - 2016 Sep 7
TI  - Androgen receptor transcriptionally regulates mu-opioid receptor expression in rat 
      trigeminal ganglia.
PG  - 52-61
LID - S0306-4522(16)30253-6 [pii]
LID - 10.1016/j.neuroscience.2016.06.023 [doi]
AB  - The involvement of testosterone in pain, inflammation, and analgesia has been 
      reported, but the role of androgen receptor (AR), a steroid receptor for 
      testosterone, is not well understood. We have previously shown that peripheral 
      inflammation upregulates mu-opioid receptor (MOR) in rat trigeminal ganglia (TG) 
      in a testosterone-dependent manner. In this study, we hypothesized that 
      testosterone regulates MOR expression via transcriptional activities of AR in TG. 
      We first examined whether AR is co-expressed with MOR in TG neurons. Our 
      immunohistochemical experiment revealed that AR staining is detected in neurons 
      of all sizes in TG and that a subset of AR is expressed in MOR as well as in 
      TRPV1-positive neurons. We identified the promoter region of the rat MOR gene 
      contains putative AR binding sites. Using chromatin immunoprecipitation assay, we 
      demonstrated that AR directly binds to these sites in TG extracts. We confirmed 
      with luciferase reporter assay that AR activated the MOR promoter in response to 
      androgens in a human neuroblastoma cell line (5H-5YSY). These data demonstrated 
      that AR functions as a transcriptional regulator of the MOR gene activity. 
      Finally, we showed that flutamide, a specific AR antagonist, prevents complete 
      Freund's adjuvant (CFA)-induced upregulation of MOR mRNA in TG, and that 
      flutamide dose-dependently blocks the efficacy of DAMGO, a specific MOR agonist, 
      on CFA-induced mechanical hypersensitivity. Our results expand the knowledge 
      regarding the role of androgens and their receptor in pain and analgesia and have 
      important clinical implications, particularly for inflammatory pain patients with 
      low or compromised plasma testosterone levels.
CI  - Copyright (c) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Lee, Ki Seok
AU  - Lee KS
AD  - University of Maryland School of Dentistry, Department of Neural and Pain 
      Sciences, 650 W. Baltimore St., Baltimore, MD 21201, USA.
FAU - Zhang, Youping
AU  - Zhang Y
AD  - University of Maryland School of Dentistry, Department of Neural and Pain 
      Sciences, 650 W. Baltimore St., Baltimore, MD 21201, USA.
FAU - Asgar, Jamila
AU  - Asgar J
AD  - University of Maryland School of Dentistry, Department of Neural and Pain 
      Sciences, 650 W. Baltimore St., Baltimore, MD 21201, USA.
FAU - Auh, Q-Schick
AU  - Auh QS
AD  - Kyung Hee University, School of Dentistry, Department of Oral Medicine, 1 Hoegi 
      Dong, Dongdaemun Gu, Seoul, Republic of Korea.
FAU - Chung, Man-Kyo
AU  - Chung MK
AD  - University of Maryland School of Dentistry, Department of Neural and Pain 
      Sciences, 650 W. Baltimore St., Baltimore, MD 21201, USA.
FAU - Ro, Jin Y
AU  - Ro JY
AD  - University of Maryland School of Dentistry, Department of Neural and Pain 
      Sciences, 650 W. Baltimore St., Baltimore, MD 21201, USA; Kyung Hee University, 
      School of Dentistry, Department of Oral Medicine, 1 Hoegi Dong, Dongdaemun Gu, 
      Seoul, Republic of Korea. Electronic address: jro@umaryland.edu.
LA  - eng
GR  - R01 DE019448/DE/NIDCR NIH HHS/United States
GR  - R01 DE023846/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160616
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Androgen Receptor Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Receptors, Opioid, mu)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Trpv1 protein, rat)
RN  - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-)
RN  - 76W6J0943E (Flutamide)
RN  - 9007-81-2 (Freund's Adjuvant)
SB  - IM
MH  - Analgesics, Opioid/pharmacology
MH  - Androgen Receptor Antagonists/pharmacology
MH  - Animals
MH  - Cell Line, Tumor
MH  - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology
MH  - Flutamide/pharmacology
MH  - Freund's Adjuvant
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Hyperalgesia/drug therapy/metabolism
MH  - Male
MH  - RNA, Messenger/metabolism
MH  - Rats, Sprague-Dawley
MH  - Receptors, Androgen/*metabolism
MH  - Receptors, Opioid, mu/agonists/*metabolism
MH  - TRPV Cation Channels/metabolism
MH  - Trigeminal Ganglion/drug effects/*metabolism
PMC - PMC5498154
MID - NIHMS872582
OTO - NOTNLM
OT  - flutamide
OT  - inflammation
OT  - peripheral
OT  - sensory neurons
OT  - testosterone
COIS- CONFLICT OF INTEREST There are no conflicts of interest associated with the 
      present study
EDAT- 2016/06/21 06:00
MHDA- 2017/07/14 06:00
PMCR- 2017/07/05
CRDT- 2016/06/21 06:00
PHST- 2016/04/15 00:00 [received]
PHST- 2016/06/06 00:00 [revised]
PHST- 2016/06/11 00:00 [accepted]
PHST- 2016/06/21 06:00 [entrez]
PHST- 2016/06/21 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2017/07/05 00:00 [pmc-release]
AID - S0306-4522(16)30253-6 [pii]
AID - 10.1016/j.neuroscience.2016.06.023 [doi]
PST - ppublish
SO  - Neuroscience. 2016 Sep 7;331:52-61. doi: 10.1016/j.neuroscience.2016.06.023. Epub 
      2016 Jun 16.