PMID- 20138435
OWN - NLM
STAT- MEDLINE
DCOM- 20101112
LR  - 20220105
IS  - 1873-3360 (Electronic)
IS  - 0306-4530 (Print)
IS  - 0306-4530 (Linking)
VI  - 35
IP  - 7
DP  - 2010 Aug
TI  - Estradiol-induced desensitization of 5-HT1A receptor signaling in the 
      paraventricular nucleus of the hypothalamus is independent of estrogen 
      receptor-beta.
PG  - 1023-33
LID - 10.1016/j.psyneuen.2010.01.003 [doi]
AB  - Estradiol regulates serotonin 1A (5-HT(1A)) receptor signaling. Since 
      desensitization of 5-HT(1A) receptors may be an underlying mechanism by which 
      selective serotonin reuptake inhibitors (SSRIs) mediate their therapeutic effects 
      and combining estradiol with SSRIs enhances the efficacy of the SSRIs, it is 
      important to determine which estrogen receptors are capable of desensitizating 
      5-HT(1A) receptor function. We previously demonstrated that selective activation 
      of the estrogen receptor, GPR30, desensitizes 5-HT(1A) receptor signaling in rat 
      hypothalamic paraventricular nucleus (PVN). However, since estrogen receptor-beta 
      (ERbeta), is highly expressed in the PVN, we investigated the role of ERbeta in 
      estradiol-induced desensitization of 5-HT(1A) receptor signaling. We first showed 
      that a selective ERbeta agonist, diarylpropionitrile (DPN) has a 100-fold lower 
      binding affinity than estradiol for GPR30. Administration of DPN did not 
      desensitize 5-HT(1A) receptor signaling in rat PVN as demonstrated by 
      agonist-stimulated hormone release. Second, we used a recombinant adenovirus 
      containing ERbeta siRNAs to decrease ERbeta expression in the PVN. Reductions in 
      ERbeta did not alter the estradiol-induced desensitization of 5-HT(1A) receptor 
      signaling in oxytocin cells. In contrast, in animals with reduced ERbeta, 
      estradiol administration, instead of producing desensitization, augmented the 
      ACTH response to a 5-HT(1A) agonist. Combined with the results from the DPN 
      treatment experiments, desensitization of 5-HT(1A) receptor signaling does not 
      appear to be mediated by ERbeta in oxytocin cells, but that ERbeta, together with 
      GPR30, may play a complex role in central regulation of 5-HT(1A)-mediated ACTH 
      release. Determining the mechanisms by which estrogens induce desensitization may 
      aid in the development of better treatments for mood disorders.
CI  - Copyright 2010 Elsevier Ltd. All rights reserved.
FAU - Rossi, Dania V
AU  - Rossi DV
AD  - Department of Pharmacology and Toxicology, School of Pharmacy, University of 
      Kansas, Lawrence, KS 66045, USA.
FAU - Dai, Ying
AU  - Dai Y
FAU - Thomas, Peter
AU  - Thomas P
FAU - Carrasco, Gonzalo A
AU  - Carrasco GA
FAU - DonCarlos, Lydia L
AU  - DonCarlos LL
FAU - Muma, Nancy A
AU  - Muma NA
FAU - Li, Qian
AU  - Li Q
LA  - eng
GR  - R01 MH058448/MH/NIMH NIH HHS/United States
GR  - R01 MH058448-10/MH/NIMH NIH HHS/United States
GR  - R01 MH058448-11/MH/NIMH NIH HHS/United States
GR  - MH058448/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100206
PL  - England
TA  - Psychoneuroendocrinology
JT  - Psychoneuroendocrinology
JID - 7612148
RN  - 0 (2,3-bis(4-hydroxyphenyl)-propionitrile)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Gper1 protein, rat)
RN  - 0 (Nitriles)
RN  - 0 (Propionates)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 4TI98Z838E (Estradiol)
RN  - 50-56-6 (Oxytocin)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
SB  - IM
MH  - Adrenocorticotropic Hormone/blood/metabolism
MH  - Animals
MH  - Estradiol/*metabolism/pharmacology
MH  - Estrogen Receptor beta/*drug effects/*metabolism
MH  - Female
MH  - Nitriles/pharmacology
MH  - Oxytocin/blood/metabolism
MH  - Paraventricular Hypothalamic Nucleus/*drug effects/*metabolism
MH  - Propionates/pharmacology
MH  - RNA, Small Interfering/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Serotonin, 5-HT1A/*metabolism
MH  - Receptors, G-Protein-Coupled/metabolism
PMC - PMC2891004
MID - NIHMS177835
EDAT- 2010/02/09 06:00
MHDA- 2010/11/13 06:00
PMCR- 2011/08/01
CRDT- 2010/02/09 06:00
PHST- 2009/07/28 00:00 [received]
PHST- 2009/11/24 00:00 [revised]
PHST- 2010/01/08 00:00 [accepted]
PHST- 2010/02/09 06:00 [entrez]
PHST- 2010/02/09 06:00 [pubmed]
PHST- 2010/11/13 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - S0306-4530(10)00018-1 [pii]
AID - 10.1016/j.psyneuen.2010.01.003 [doi]
PST - ppublish
SO  - Psychoneuroendocrinology. 2010 Aug;35(7):1023-33. doi: 
      10.1016/j.psyneuen.2010.01.003. Epub 2010 Feb 6.