Thyrotropin (TSH)-secreting
pituitary adenomas cause
hyperthyroxinemia in the presence of "inappropriately" elevated concentrations of TSH. TSH production under these circumstances escapes the normal negative feedback effect of
thyroid hormone. We propose that this defective negative feedback is mediated by an abnormality of
thyroid hormone receptor (TR) expression. Two TSH-secreting
pituitary adenomas were analyzed by immunocytochemistry for TR
isoform protein expression and by semiquantitative
reverse transcriptase polymerase chain reaction (RT-PCR) for TR
isoform mRNA expression. The results obtained from these
tumors were compared with the findings from six normal human pituitaries. Neither
tumor examined expressed detectable levels of nuclear TRalpha or TRbeta
proteins, in contrast to the normal pituitaries studied, which expressed all TR
isoforms. Application of RT-PCR, however, revealed mRNAs encoding each TR
isoform in all tumorous and normal tissues examined. Semiquantitative RT-PCR revealed similar levels of expression of TRalpha and TRbeta
isoform mRNAs in
tumors and normal tissue, in contrast to the observed difference in TR
proteins. Absent TRalpha and TRbeta
protein expression, in association with normal
mRNA levels, implies a post-transcriptional defect in TR
mRNA processing in TSH-secreting
adenomas. Reduced TR expression in these
tumors may explain defective negative feedback of
thyroid hormone on TSH production, and may also contribute to uncontrolled
tumor growth.