PMID- 11897691
OWN - NLM
STAT- MEDLINE
DCOM- 20020429
LR  - 20161124
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 143
IP  - 4
DP  - 2002 Apr
TI  - Steroid receptor coactivator-1 deficiency causes variable alterations in the 
      modulation of T(3)-regulated transcription of genes in vivo.
PG  - 1346-52
AB  - Thyroid hormone exerts its biological effect by binding to a TR. Both liganded 
      and unliganded TRs regulate the transcription of T(3)-responsive genes. Cofactors 
      with activating or repressing function modulate the transcriptional regulation by 
      TRs. We showed that steroid receptor coactivator 1 (SRC-1)-deficient mice 
      (SRC-1(-/-)) exhibit partial resistance to thyroid hormone at the level of the 
      pituitary thyrotrophs. To determine whether SRC-1 deficiency affects globally 
      T(3)-dependent transcriptional regulation, we studied the effects of thyroid 
      hormone deprivation and replacement on the expression of several genes in 
      different tissues of SRC-1(-/-) and wild-type mice (SRC-1(+/+)). Thyroid hormone 
      deficiency was induced by a low iodine diet (LoI) supplemented with 
      propylthiouracil (PTU) for 2 wk. L-T(3) was injected ip for the last 4 d in one 
      group (PTU+T(3) group), and another group (PTU group) received only vehicle. 
      Levels of mRNAs for T(3)-responsive genes were determined by Northern blotting: 
      GH and TSH beta in pituitary; type 1 iodothyronine 5'-deiodinase, spot 14 (S14), 
      and malic enzyme in liver; and sarcoplasmic reticulum calcium adenosine 
      triphosphatase 2 and myosin heavy chain alpha and beta in heart. Serum 
      parameters, TSH, total cholesterol, creatine kinase, and alkaline phosphatase 
      (AP), were also measured. Hypothyroidism produced a comparable increase in TSH 
      beta mRNA in both genotypes, but its suppression by L-T(3) was attenuated in 
      SRC-1(-/-) mice. In contrast, hypothyroidism failed to reduce S14 mRNA levels in 
      SRC-1(-/-) mice. As a consequence, the response to L-T(3) was not observed in 
      these mice. SRC-1 deficiency had no effect on the expression of the rest of the 
      T(3)-responsive genes examined. Of the four serum parameters, the T(3)-mediated 
      decrease in TSH and changes in AP were attenuated in SRC-1(-/-) mice. We conclude 
      that SRC-1 deficiency altered the expression of only some of the T(3)-responsive 
      genes. SRC-1 appears to be involved not only in transcriptional activation by 
      liganded TRs, but also in the suppression by liganded or unliganded TRs. Some of 
      the effects of SRC-1 may be TR isoform specific.
FAU - Takeuchi, Yoko
AU  - Takeuchi Y
AD  - Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, 
      Japan.
FAU - Murata, Yoshiharu
AU  - Murata Y
FAU - Sadow, Peter
AU  - Sadow P
FAU - Hayashi, Yoshitaka
AU  - Hayashi Y
FAU - Seo, Hisao
AU  - Seo H
FAU - Xu, Jianming
AU  - Xu J
FAU - O'Malley, Bert W
AU  - O'Malley BW
FAU - Weiss, Roy E
AU  - Weiss RE
FAU - Refetoff, Samuel
AU  - Refetoff S
LA  - eng
GR  - DK-15070/DK/NIDDK NIH HHS/United States
GR  - DK-58242/DK/NIDDK NIH HHS/United States
GR  - DK-58258/DK/NIDDK 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.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Hormones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 9002-71-5 (Thyrotropin)
RN  - 9002-72-6 (Growth Hormone)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/blood/genetics
MH  - Animals
MH  - Blotting, Northern
MH  - Cholesterol/blood/genetics
MH  - Creatine Kinase/biosynthesis/genetics
MH  - Gene Expression Regulation/*genetics/*physiology
MH  - Growth Hormone/biosynthesis
MH  - Histone Acetyltransferases
MH  - Hormones/biosynthesis/blood/genetics
MH  - Hypothyroidism/chemically induced/metabolism
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Myocardium/metabolism
MH  - Nuclear Receptor Coactivator 1
MH  - Pituitary Gland/metabolism
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Thyrotropin/biosynthesis/blood
MH  - Transcription Factors/deficiency/*genetics
MH  - Triiodothyronine/*genetics/*physiology
EDAT- 2002/03/19 10:00
MHDA- 2002/05/01 10:01
CRDT- 2002/03/19 10:00
PHST- 2002/03/19 10:00 [pubmed]
PHST- 2002/05/01 10:01 [medline]
PHST- 2002/03/19 10:00 [entrez]
AID - 10.1210/endo.143.4.8730 [doi]
PST - ppublish
SO  - Endocrinology. 2002 Apr;143(4):1346-52. doi: 10.1210/endo.143.4.8730.