THYROID-HORMONE UP-REGULATES THYROID-HORMONE RECEPTOR BETA-GENE EXPRESSION IN RAT CEREBRAL HEMISPHERE ASTROCYTE CULTURES

Oligonucleotide probes complementary to specific regions of three thyr oid receptor cDNAs were used to study the effects of thyroid hormone o n the expression of the mRNAs encoding two alpha (alpha1, and alpha2) and one beta-thyroid (beta1) receptors isoforms in rat cerebral hemisp here astrocyte cultures. Both genes are expressed by type 1 astrocytes . The levels of the alpha1-, alpha2-, and beta1-mRNAs did not signific antly change between day 8 and day 22, in cultures grown in the absenc e of thyroid hormone. L-triiodothyronine (L-T3) treatment of the cultu res increased the levels of beta1-mRNAs by fivefold without changing e ither the levels of the alpha1- and alpha2-mRNAs or L-T3 binding capac ity. The effect of L-T3 on beta1-mRNAs was observed after 4 h of treat ment and was independent of protein synthesis, suggesting that this ef fect is likely to be a direct one. Treatment of the cultures by cytosi ne arabinosine, a drug that kills dividing cells, specifically decreas ed level of the alpha1- and alpha2-mRNAs by 60% and 38%, respectively. Finally, by immunocytochemistry, we showed that the beta1 receptor-im munoreactivity was either located in the perinuclear region and the cy toplasm or in the nuclei of astrocytes. Taken together with previous d ata obtained in neuronal cultures where no effect of L-T3 was observed on the levels of the beta1-mRNAs, our findings indicate that the beta 1 gene is differentially regulated in neurons and astrocytes. Furtherm ore, our results are also in favor of specific functions for both type s of thyroid receptors during astrocyte differentiation. (C) 1993 Wile y-Liss, Inc.