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

Oligonucleotide probes complementary to specific regions of three thyroid receptor cDNAs were used to study the effects of thyroid hormone on the expression of the mRNAs encoding two alpha (alpha1, and alpha2) and one beta-thyroid (beta1) receptors isoforms in rat cerebral hemisphere astrocyte cultures. Both genes are expressed by type 1 astrocytes. The levels of the alpha1-, alpha2-, and beta1-mRNAs did not significantly change between day 8 and day 22, in cultures grown in the absence of thyroid hormone. L-triiodothyronine (L-T3) treatment of the cultures increased the levels of beta1-mRNAs by fivefold without changing either the levels of the alpha1- and alpha2-mRNAs or L-T3 binding capacity. The effect of L-T3 on beta1-mRNAs was observed after 4 h of treatment and was independent of protein synthesis, suggesting that this effect is likely to be a direct one. Treatment of the cultures by cytosine arabinosine, a drug that kills dividing cells, specifically decreased level of the alpha1- and alpha2-mRNAs by 60% and 38%, respectively. Finally, by immunocytochemistry, we showed that the beta1 receptor-immunoreactivity was either located in the perinuclear region and the cytoplasm or in the nuclei of astrocytes. Taken together with previous data obtained in neuronal cultures where no effect of L-T3 was observed on the levels of the beta1-mRNAs, our findings indicate that the beta1 gene is differentially regulated in neurons and astrocytes. Furthermore, our results are also in favor of specific functions for both types of thyroid receptors during astrocyte differentiation. (C) 1993 Wiley-Liss, Inc.