Persistent synchronized oscillations in prolactin gene promoter activity in living pituitary cells

PRL gene expression in the anterior pituitary gland responds rapidly to dif ferent hormonal signals. We have investigated the long-term timing of trans criptional activation from the PRL, GH, and cytomegalovirus promoters in re sponse to different stimulus duration, using real-time imaging of luciferas e expression in living stably transfected GH3 cells. Long-term stimulation of serum-starved cells with 50% serum induced a homogeneous rise in PRL pro moter activity, with subsequent heterogeneous fluctuations in luciferase ac tivity in individual cells. When cells were subjected to a 2-h pulse of 50% serum, followed by serum-fi ee medium, there were long-term (approximately 50 h) synchronized, homogeneous oscillations in PRL promoter activity. Thi s response was PRL-specific, because in GH3 cells expressing luciferase fro m the GH or cytomegalovirus promoters, a serum pulse elicited no oscillatio ns in luciferase expression after an initial transient response to serum. T he PRL promoter may therefore be a template for an unstable transcription c omplex subject to stochastic regulation, allowing an oscillatory transcript ional response to physiological signals. This suggests that precise timing and coordination of cell responses to different signal-duration may represe nt a novel mechanism for coordinating long-term dynamic changes in transcri ption in cell populations.