Regulation of growth hormone gene expression: synergistic effects of thyroid and glucocorticoid hormones.

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Abstract
Cultured rat pituitary cells (GC) respond to thyroid and glucocorticoid hormones by increases in growth hormone [GH] production and GH mRNA. When these cells are transferred from medium containing normal animal serum (with 1.8 .mu.g of thyroxine per dl) to a medium containing serum from a thyroidectomized calf, hypothyroid medium (with no detectable thyroid hormone) GH production decreases markedly. In cells maintained for 5 days in hypothyroid medium, triiodothyronine induces within 50 h a 17-fold increase in GH production whereas glucocorticoids, during the same time, produce a negligible (3-fold or less) stimulation. In combination the 2 hormones promote a 45-fold stimulation. In all instances the changes in GH production are paralleled by changes in the levels of GH mRNA as measured by cell-free translation. The transfer to hypothyroid medium and the hormonal induction do not affect the relative activities of other mRNA whose products are detectable on polyacrylamide gels. Thyroid hormone probably can be an activator of the expression of the GH gene. Triidothyronine controls the magnitude of the effect of glucocorticoids on GH mRNA, and provide a model for permissive triiodothyronine action. The synergistic effect of these 2 classes of hormone suggests that they increase levels of GH mRNA by different mechanisms.