DIFFERENTIAL EXPRESSION OF THYROID-HORMONE RECEPTOR ISOFORMS IN NEURONS AND ASTROGLIAL CELLS

The brain has abundant nuclear T-3-binding sites and contains messenge r RNAs (mRNAs) encoding multiple thyroid hormone receptor (TR) isoform s; the cellular distribution of these different TR isoforms is unknown . To determine whether the TR isoforms are differentially expressed in neuronal and astroglial cells, we examined the relative abundance of the mRNAs encoding TR alpha 1, c-erbA alpha 2, and TR beta 1 in primar y cultures of fetal rat brain and in several cell lines of neural and glial origin. Additionally, the TR isoform polypeptides were identifie d by immunocytochemistry using isoform-specific antibodies. Northern b lot analysis showed that fetal brain cell cultures contain mRNAs encod ing the T-3-binding isoforms TR alpha 1 and TR beta 1 as well as the m RNA encoding the non-T-3-binding c-erbA alpha 2. c-erbA alpha 2 mRNA w as most abundant, comprising more than 85% of the TR mRNAs in the prim ary cultures. Neuronal enrichment by antimitotic selection increased T R beta 1 mRNA similar to 3-fold, decreased c-erbA alpha 2 mRNA 70%, an d had little or no effect on TR alpha 1 mRNA. Neuronal depletion resul ted in the complete loss of TR beta 1 mRNA without changing c-erb alph a 2 or TR alpha 1 mRNA levels. Primary cultures of rat astrocytes, the astrocytoma cell line C6, and the pheochromocytoma cell line PC12 con tained only the c-erbA alpha 2 mRNA. Immunocytochemistry using isoform -specific antisera revealed that TR beta 1 was exclusively localized t o neuronal nuclei, and c-erbA alpha 2 was only found in the nuclei of astrocytes. These results show that TR beta 1 is localized to the nucl ei of neuronal cells, and that c-erbA alpha 2 is restricted to the nuc lei of astrocytes.