Hormonal regulation of stability of glutamine synthetase mRNA in cultured 3T3-L1 adipocytes.

In 3T3-L1 adipocytes, glutamine synthetase (GS; EC 6.3.1.2) is subject to regulation by dexamethasone, insulin and dibutyryl cyclic AMP (Bt2cAMP). Dexamethasone increases GS-mRNA content and GS-gene transcription, whereas insulin and Bt2cAMP prevent these increases. The effects of these modulators on the control of GS-mRNA stability were investigated. We report here that GS mRNA has a half-life of about 110 min. Bt2cAMP increases GS-mRNA degradation by greater than 2-fold (half-life 50 min), whereas insulin or dexamethasone have little effect on GS-mRNA stability. Down-regulation of GS-gene expression by Bt2cAMP will involve a co-ordinate response at the level of gene transcription and mRNA stability. However, the molecular mechanisms by which insulin and dexamethasone regulate GS-gene expression in cultured adipocytes remains to be elucidated.