Hormonal Regulation of Growth Hormone mRNA

Abstract

Production of growth hormone by cultured rat pituitary tumor cells (GH₃ subline) is regulated by hormones. In previous studies, it was shown that thyroid and glucocorticoid hormones stimulate growth hormone synthesis. In the current studies, a cloned cDNA probe complementary to growth hormone mRNA was used to determine, by solution hybridization, the number of growth hormone mRNA molecules per cell under various hormonal conditions. The experiments were performed with cells grown in three different medium conditions to distinguish the effect of the added hormones from the effect of serum factors. The results show that, within 72 h, both thyroid and glucocorticoid hormones, when added alone, are able to induce a significant accumulation of cytoplasmic growth hormone mRNA. However, to obtain their maximal efficiencies, the two types of hormones have different requirements: glucocorticoids appear to need only the presence of thyroid hormones, whereas thyroid hormones appear to require some as yet unidentified serum factors. When added together, the two classes of hormones act synergistically. The maximal range of growth hormone mRNA in these cells varies by over 500-fold—from about 1000 molecules per cell (10% calf serum plus thyroid and glucocorticoid hormones) to less than two molecules per cell (in a defined serum-substitute-containing medium with no hormone added). The data further suggest that, in these GH₃ cells, the efficiency of translation of growth hormone mRNA can also vary (by a factor of 4), depending on the hormonal conditions used. However, these latter influences are not specific for growth hormone mRNA but rather appear to be a general translational effect on all the mRNA population. These results demonstrate that the major effect of thyroid and glucocorticoid hormones on growth hormone production is due to effects on the number of growth hormone mRNA molecules.