REGULATION OF GROWTH-HORMONE MESSENGER-RNA SYNTHESIS BY DEXAMETHASONE AND TRIIODOTHYRONINE - TRANSCRIPTIONAL RATE AND MESSENGER-RNA STABILITY CHANGES IN PITUITARY-TUMOR CELLS

The process was characterized by which the growth hormone (GH) gene is stimulated in rat pituitary tumor cells (GC or GH3) by the steroid hormone dexamethasone (Dex) and the thyroid hormone, L-triiodothyronine (T3). A primary transcriptional response is detected within 60 min of addition of T3 or Dex + T3 to GH-producing cells (GC or GH3). A 5-fold transcriptional stimulation of GH nuclear RNA occurs in cells cultured with serum substitute medium and induced with Dex + T3, while T3 alone induces a modest 2-3 fold stimulation. The absence of fetal calf serum from the cell culture medium does not decrease the level of transcriptional activity of the GH gene during hormone stimulation. After (24 h) addition of Dex + T3 the cytoplasmic GH mRNA shows a 50-fold increase, as measured by S1 nuclease analysis. This large accumulation of cytoplasmic GH mRNA in contrast to the relatively small changes in GH gene activity is inconsistent with solely a transcriptional mechanism of hormone induction. A change in specific GH mRNA stability may also take plase in response to Dex + T3. Transcriptional stimulation of the GH gene by Dex is insignificant except in the presence of T3.