PMID- 26223010
OWN - NLM
STAT- MEDLINE
DCOM- 20160119
LR  - 20181202
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 154
DP  - 2015 Nov
TI  - Steroid receptor coactivator-1 mediates letrozole induced downregulation of 
      postsynaptic protein PSD-95 in the hippocampus of adult female rats.
PG  - 168-75
LID - S0960-0760(15)30024-8 [pii]
LID - 10.1016/j.jsbmb.2015.07.011 [doi]
AB  - Hippocampus local estrogen which is converted from androgen that catalyzed by 
      aromatase has been shown to play important roles in the regulation of learning 
      and memory as well as cognition through action on synaptic plasticity, but the 
      underlying mechanisms are poorly understood. Steroid receptor coactivator-1 
      (SRC-1) is one of the coactivators of steroid nuclear receptors; it is widely 
      distributed in brain areas that related to learning and memory, reproductive 
      regulation, sensory and motor information integration. Previous studies have 
      revealed high levels of SRC-1 immunoreactivities in the hippocampus; it is 
      closely related to the levels of synaptic proteins such as PSD-95 under normal 
      development or gonadectomy, but its exact roles in the regulation of these 
      proteins remains unclear. In this study, we used aromatase inhibitor letrozole in 
      vivo and SRC-1 RNA interference in vitro to investigate whether SRC-1 mediated 
      endogenous estrogen regulation of hippocampal PSD-95. The results revealed that 
      letrozole injection synchronously decreased hippocampal SRC-1 and PSD-95 in a 
      dose-dependant manner. Furthermore, when SRC-1 specific shRNA pool was applied to 
      block the expression of SRC-1 in the primary hippocampal neuron culture, both 
      immunocytochemistry and Western blot revealed that levels of PSD-95 were also 
      decreased significantly. Taking together, these results provided the first 
      evidence that SRC-1 mediated endogenous estrogen regulation of hippocampal 
      synaptic plasticity by targeting the expression of synaptic protein PSD-95. 
      Additionally, since letrozole is frequently used to treat estrogen-sensitive 
      breast cancer, the above results also indicate its potential side effects in 
      clinical administration.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Liu, Mengying
AU  - Liu M
AD  - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third 
      Military Medical University, Chongqing 400038, China; Cadet Brigade, Third 
      Military Medical University, Chongqing 400038, China.
FAU - Huangfu, Xuhong
AU  - Huangfu X
AD  - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third 
      Military Medical University, Chongqing 400038, China; Cadet Brigade, Third 
      Military Medical University, Chongqing 400038, China.
FAU - Zhao, Yangang
AU  - Zhao Y
AD  - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third 
      Military Medical University, Chongqing 400038, China.
FAU - Zhang, Dongmei
AU  - Zhang D
AD  - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third 
      Military Medical University, Chongqing 400038, China; Department of Dermatology, 
      Southwest Hospital, Third Military Medical University, Chongqing 400038, China. 
      Electronic address: 574235375@qq.com.
FAU - Zhang, Jiqiang
AU  - Zhang J
AD  - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third 
      Military Medical University, Chongqing 400038, China. Electronic address: 
      zhangjqtmmu@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150726
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nitriles)
RN  - 0 (Triazoles)
RN  - 7LKK855W8I (Letrozole)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
SB  - IM
MH  - Animals
MH  - Aromatase Inhibitors/*pharmacology
MH  - Cells, Cultured
MH  - Disks Large Homolog 4 Protein
MH  - Down-Regulation/*drug effects
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Hippocampus/*drug effects/metabolism
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Letrozole
MH  - Membrane Proteins/*metabolism
MH  - Nitriles/*pharmacology
MH  - Nuclear Receptor Coactivator 1/genetics/*physiology
MH  - RNA Interference
MH  - Rats
MH  - Rats, Wistar
MH  - Triazoles/*pharmacology
OTO - NOTNLM
OT  - Aromatase
OT  - Estrogens
OT  - Hippocampus
OT  - Steroid receptor coactivator-1
OT  - Synaptic plasticity
EDAT- 2015/07/30 06:00
MHDA- 2016/01/20 06:00
CRDT- 2015/07/30 06:00
PHST- 2015/03/03 00:00 [received]
PHST- 2015/07/20 00:00 [revised]
PHST- 2015/07/22 00:00 [accepted]
PHST- 2015/07/30 06:00 [entrez]
PHST- 2015/07/30 06:00 [pubmed]
PHST- 2016/01/20 06:00 [medline]
AID - S0960-0760(15)30024-8 [pii]
AID - 10.1016/j.jsbmb.2015.07.011 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2015 Nov;154:168-75. doi: 
      10.1016/j.jsbmb.2015.07.011. Epub 2015 Jul 26.