EXPRESSION OF HSP90-BETA MESSENGER-RIBONUCLEIC-ACID IN PATIENTS WITH FAMILIAL GLUCOCORTICOID RESISTANCE CORRELATION TO RECEPTOR STATUS

We have previously shown an increased specific DNA-binding of liganded unactivated glucocorticoid receptor (GR) to the LTR-region of MMTV DN A in a patient with primary cortisol resistance and receptor thermolab ility indicating a defective interaction of GR with hsp90. In some pat ients, however, no apparent receptor abnormality was found in spite of a characteristic phenotype. mRNA expression levels of hsp90 beta were analysed in cultured fibroblasts from patients with known receptor de fects, such as thermolability, decreased ligand binding affinity and l ow receptor expression levels, and from patients with a cortisol resis tant phenotype but no detected receptor alteration. Fibroblasts from p atients with GR defects expressed higher hsp90 beta mRNA levels as com pared to patients with no receptor defects or to healthy controls. The se data indicate that GR defects are associated with increased hsp90 b eta mRNA levels.