Retinoid X receptor expression in the normal pituitary and clinically 'non-functioning' pituitary tumours

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Abstract

OBJECTIVE

The glycoprotein hormone common α-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 α-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 α-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

RXRα was expressed in a similar proportion (approximately 50%) of both normal human pituitaries and NFTs, while RXRβ and γ 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 RXRα and RXRβ isoforms in normals and NFTs but significantly reduced expression of RXRγ 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 α-subunit production.

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