PMID- 12576486
OWN - NLM
STAT- MEDLINE
DCOM- 20040617
LR  - 20161124
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 17
IP  - 5
DP  - 2003 May
TI  - Thyroid hormone receptor-specific interactions with steroid receptor 
      coactivator-1 in the pituitary.
PG  - 882-94
AB  - Steroid receptor coactivator-1 (SRC-1) is a transcription cofactor that enhances 
      the hormone-dependent action mediated by the thyroid hormone (TH) receptor (TR) 
      as well as other nuclear receptors. However, it is not known whether the 
      SRC-1-mediated activation of TH-regulated gene transcription is TR isoform 
      specific in the pituitary. We generated mice that were deficient in TRalpha and 
      SRC-1 (TRalpha(0/0)SRC-1(-/-)), as well in TRbeta and SRC-1 
      (TRbeta(-/-)SRC-1(-/-)), and thyroid function tests and effects of TH deprivation 
      and TH treatment were compared with wild-type mice or mice with deletion of 
      either TRs or SRC-1 alone. We have shown that 1) TRbeta(-/-)SRC-1(-/-) mice 
      demonstrate more severe TH resistance than either the SRC-1(-/-) or TRbeta(-/-) 
      mice; the additive effect indicates that SRC-1 has an independent role in TH 
      action over that of TRbeta; 2) SRC-1 facilitates TRbeta and TRalpha-mediated 
      down-regulation of TSH, as TRalpha(0/0)SRC-1(-/-) mice demonstrate TH resistance 
      rather than hypersensitivity as seen in TRalpha(0/0)mice; and 3) a compensatory 
      increase in SRC-1 expression is associated with the TH hypersensitivity seen in 
      TRalpha-deficient animals. We conclude that SRC-1 action in the pituitary 
      mediates TH action via specific TR subtypes.
FAU - Sadow, Peter M
AU  - Sadow PM
AD  - Department of Medicine, University of Chicago, Illinois, USA.
FAU - Koo, Eugene
AU  - Koo E
FAU - Chassande, Olivier
AU  - Chassande O
FAU - Gauthier, Karine
AU  - Gauthier K
FAU - Samarut, Jacques
AU  - Samarut J
FAU - Xu, Jianming
AU  - Xu J
FAU - O'Malley, Bert W
AU  - O'Malley BW
FAU - Seo, Hisao
AU  - Seo H
FAU - Murata, Yoshiharu
AU  - Murata Y
FAU - Weiss, Roy E
AU  - Weiss RE
LA  - eng
GR  - DK-58242/DK/NIDDK NIH HHS/United States
GR  - DK-58281/DK/NIDDK NIH HHS/United States
GR  - HD-078587/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030206
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Nuclear Receptor Coactivator 2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Thyroid Hormone Receptors alpha)
RN  - 0 (Thyroid Hormone Receptors beta)
RN  - 0 (Thyroid Hormones)
RN  - 0 (Thyrotropin, beta Subunit)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 9002-71-5 (Thyrotropin)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Ncoa3 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 3)
SB  - IM
MH  - Animals
MH  - Cell Nucleus/metabolism
MH  - Female
MH  - Histone Acetyltransferases
MH  - Male
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Nuclear Receptor Coactivator 1
MH  - Nuclear Receptor Coactivator 2
MH  - Nuclear Receptor Coactivator 3
MH  - Pituitary Gland/drug effects/*physiology
MH  - RNA, Messenger/drug effects
MH  - Receptors, Thyroid Hormone/genetics/*metabolism
MH  - Thyroid Function Tests
MH  - Thyroid Hormone Receptors alpha/genetics/*metabolism
MH  - Thyroid Hormone Receptors beta
MH  - Thyroid Hormone Resistance Syndrome/drug therapy/genetics/metabolism
MH  - Thyroid Hormones/deficiency/metabolism/pharmacology
MH  - Thyrotropin/blood/genetics/metabolism
MH  - Thyrotropin, beta Subunit/drug effects/genetics
MH  - Trans-Activators/genetics/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Triiodothyronine/metabolism
EDAT- 2003/02/11 04:00
MHDA- 2004/06/18 05:00
CRDT- 2003/02/11 04:00
PHST- 2003/02/11 04:00 [pubmed]
PHST- 2004/06/18 05:00 [medline]
PHST- 2003/02/11 04:00 [entrez]
AID - me.2002-0174 [pii]
AID - 10.1210/me.2002-0174 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2003 May;17(5):882-94. doi: 10.1210/me.2002-0174. Epub 2003 Feb 
      6.