GLUTAMINE-SYNTHETASE EXPRESSION AND ACTIVITY ARE REGULATED BY 3,5,3'-TRIODO-L-THYRONINE AND HYDROCORTISONE IN RAT OLIGODENDROCYTE CULTURES

Glutamine synthetase plays a central role in the detoxification of bra in ammonia. Previously, we demonstrated that in vitro glutamine synthe tase is expressed by all macroglial cell types and is developmentally regulated in oligodendrocyte lineage. Furthermore, glutamine synthetas e is increased in secondary cultures of oligodendrocytes following a 7 2 h treatment with 30 nM 3,5,3'-triodo-L-thyronine [Baas, D., Bourbeau , D., Sarlieve, L. L., Ittel, M. E., Dussault, J. H. and Puymirat, J., Oligodendrocyte maturation and progenitor cell proliferation are inde pendently regulated by thyroid hormone. Glia, 1997, 19, 324-332]. Hydr ocortisone also increases glutamine synthetase activity after 72 h [Fr essinaud, C., Weinrauder, H., Delaunoy, J. P., Tholey, G., Labourdette , G. and Sarlieve, L. L., Glutamine synthetase expression in rat oligo dendrocytes in culture: regulation by hormones and growth factors. J. Cell. Physiol., 1991, 149, 459-468]; however, it is still unknown whet her these increases in glutamine synthetase expression in oliorodendro cytes after 3,5,3'-triodo-L-thyronine and hydrocortisone application a re dose- and time-dependent. To further investigate this issue, we mea sured glutamine synthetase levels by Northern analysis, immunostaining and determination of glutamine synthetase activity after 3,5,3'-triod o-L-thyronine or hydrocortisone stimulation. We find that in rat oligo dendrocyte secondary cultures, 3,5,3'-triodo-L-thyronine and hydrocort isone cause a dose- and time-dependent increase in glutamine synthetas e mRNA, protein and activity. However. these hormones do not exert an additive or synergistic effect. Because purines, pyrimidines, and cert ain amino acids necessary for the synthesis of myelin components. are, in part, provided by the glutamine synthetase pathway, 3,5,3'-triodo- L-thyronine effect on myelination development and maturation could be mediated in part, through the glutamine synthetase gene regulation. (C ) 1998 ISDN. Published by Elsevier Science Ltd.