Cyclic regulation of growth hormone gene transcription in vivo and in vitro.

Abstract

The in vivo thyroid and glucocorticoid hormone regulation of GH gene transcription was compared with that found in cultured GH rat pituitary tumor cells. The GH cell lines have been widely used to study GH gene expression, but their relevance to the in vivo regulation of the gene has not been well established. The in vivo studies described here utilized rats that were both thyroparathyroidectomized and adrenalectomized to remove the organ sources of these hormones. The in vitro studies described utilized GC cells hormonally deinduced in medium lacking the hormones. Continuous administration of glucocorticoid or thyroid hormones to either system induced multiple cycles of GH transcriptional activation and deactivation. These cycles were accompanied by cycles of increasing and decreasing GH messenger RNA. In both systems, a brief transcription cycle occurred within hours of thyroid or glucocorticoid hormone addition, and a second broad occurred between 3 and 11 days later. These cycles were independent of changes in receptor levels. The similarities in the responses found in vivo and in cell culture suggest that the molecular mechanisms regulating expression of the GH gene appropriately function in GC cells, despite their transformed phenotype and prolonged maintenance in culture. Thus, these cell lines appear to be appropriate model systems for studies of thyroid and glucocorticoid hormone action.