PMID- 9640409
OWN - NLM
STAT- MEDLINE
DCOM- 19980723
LR  - 20190813
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 48
IP  - 4
DP  - 1998 Apr
TI  - Retinoid X receptor expression in the normal pituitary and clinically 
      'non-functioning' pituitary tumours.
PG  - 425-33
AB  - OBJECTIVE: The glycoprotein hormone common alpha-subunit is frequently expressed 
      in clinically 'non-functioning' tumours (NFTs) of the anterior pituitary, despite 
      normal levels of T3 and gonadal steroids. This observation suggests abnormal 
      negative-feedback regulation of the alpha-subunit by T3 and gonadal steroids in 
      NFTs. We have previously documented reduced expression of thyroid hormone 
      receptor (TR) variants in NFTs compared to normals and proposed that this 
      observation may, in part, explain the defective negative regulation. Due to the 
      important role of retinoid X receptors (RXRs) in transactivating TR-mediated 
      transcriptional regulation, via heterodimer formation, we hypothesize that 
      aberrant RXR isoform expression in NFTs may contribute to the defective negative 
      regulation of the alpha-subunit by T3. DESIGN: Comparison of RXR isoform protein 
      and mRNA expression in NFTs and normal pituitaries. PATIENTS AND TUMOURS: Twenty 
      clinically non-functioning pituitary tumours and 27 normal pituitaries were 
      obtained for analysis. MEASUREMENTS: Immunocytochemistry and semiquantitative 
      RT-PCR was performed on tumours and normal pituitaries to determine the relative 
      levels of expression of RXR isoform proteins and mRNAs, respectively. RESULTS: 
      RXR alpha was expressed in a similar proportion (approximately 50%) of both 
      normal human pituitaries and NFTs, while RXR beta and gamma were each observed in 
      26% of normals but were undetectable in NFTs. The application of semiquantitative 
      RT-PCR revealed similar levels of mRNAs encoding the RXR alpha and RXR beta 
      isoforms in normals and NFTs but significantly reduced expression of RXR gamma 
      mRNA was observed in NFTs. CONCLUSIONS: We propose that abnormal RXR isoform 
      expression in clinically 'non-functioning' pituitary tumours may contribute to 
      abnormal T3-mediated negative regulation of alpha-subunit production.
FAU - Gittoes, N J
AU  - Gittoes NJ
AD  - Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, UK. 
      n.j.gittoes@bham.ac.uk
FAU - McCabe, C J
AU  - McCabe CJ
FAU - Verhaeg, J
AU  - Verhaeg J
FAU - Sheppard, M C
AU  - Sheppard MC
FAU - Franklyn, J A
AU  - Franklyn JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - DNA-Binding Proteins/*analysis/genetics
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Isomerism
MH  - Male
MH  - Middle Aged
MH  - Pituitary Gland/*chemistry
MH  - Pituitary Neoplasms/*chemistry
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/analysis
MH  - Receptors, Retinoic Acid/*analysis/genetics
MH  - Retinoid X Receptors
MH  - Transcription Factors/*analysis/genetics
EDAT- 1998/06/26 00:00
MHDA- 1998/06/26 00:01
CRDT- 1998/06/26 00:00
PHST- 1998/06/26 00:00 [pubmed]
PHST- 1998/06/26 00:01 [medline]
PHST- 1998/06/26 00:00 [entrez]
AID - 10.1046/j.1365-2265.1998.00339.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 1998 Apr;48(4):425-33. doi: 
      10.1046/j.1365-2265.1998.00339.x.