RETINOID-X-RECEPTOR EXPRESSION IN THE NORMAL PITUITARY AND CLINICALLYNONFUNCTIONING PITUITARY-TUMORS

OBJECTIVE The glycoprotein hormone common alpha-subunit is frequently expressed in clinically 'non-functioning' tumours (NFTs) of the anteri or pituitary, despite normal levels of T3 and gonadal steroids. This o bservation suggests abnormal negative-feedback regulation of the alpha -subunit by T3 and gonadal steroids in NFTs. We have previously docume nted reduced expression of thyroid hormone receptor (TR) variants in N FTs compared to normals and proposed that this observation may, in par t, explain the defective negative regulation. Due to the important rol e of retinoid X receptors (RXRs) in transactivating TR-mediated transc riptional regulation, via heterodimer formation, we hypothesize that a berrant 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 tum ours and 27 normal pituitaries were obtained for analysis. MEASUREMENT S Immunocytochemistry and semiquantitative RT-PCR was performed on tum ours and normal pituitaries to determine the relative levels of expres sion of RXR isoform proteins and mRNAs, respectively. RESULTS RXR alph a was expressed in a similar proportion (approximately 50%) of both no rmal human pituitaries and NFTs, while RXR beta and gamma were each ob served in 26% of normals but were undetectable in NFTs, The applicatio n of semiquantitative RT-PCR revealed similar levels of mRNAs encoding the RXR alpha and RXR beta isoforms in normals and NFTs but significa ntly reduced expression of RXR gamma mRNA was observed in NFTs. CONCLU SIONS We propose that abnormal RXR isoform expression in clinically 'n on-functioning' pituitary tumours may contribute to abnormal T3-mediat ed negative regulation of alpha-subunit production.