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Persistent Synchronized Oscillations in Prolactin Gene Promoter Activity in Living Pituitary Cells¹

School of Biological Sciences (D.W.M., Z.C.S., M.R.H.W.), Life Sciences Building, University of Liverpool, Liverpool, L69 7ZB; Endocrine Sciences Research Group (D.W.M., A.J.N., R.A.K., N.T., M.S.G., W.R.R., J.R.E.D.), Faculty of Medicine, University of Manchester, Manchester, M13 9PT; and School of Biological Sciences (J.A.S., A.S.I.L.), University of Manchester, Manchester, M13 9PT, United Kingdom

Address all correspondence and requests for reprints to: M. R. H. White, School of Biological Sciences, Life Sciences Building, University of Liverpool, Crown Street, Liverpool, L69 7ZB, United Kingdom ( E-mail: mwhite{at}liv.ac.uk) or to J. R. E.

PRL gene expression in the anterior pituitary gland responds rapidly to different hormonal signals. We have investigated the long-term timing of transcriptional activation from the PRL, GH, and cytomegalovirus promoters in response to different stimulus duration, using real-time imaging of luciferase expression in living stably transfected GH3 cells. Long-term stimulation of serum-starved cells with 50% serum induced a homogeneous rise in PRL promoter activity, with subsequent heterogeneous fluctuations in luciferase activity in individual cells. When cells were subjected to a 2-h pulse of 50% serum, followed by serum-free medium, there were long-term (approximately 50 h) synchronized, homogeneous oscillations in PRL promoter activity. This response was PRL-specific, because in GH3 cells expressing luciferase from the GH or cytomegalovirus promoters, a serum pulse elicited no oscillations in luciferase expression after an initial transient response to serum. The PRL promoter may therefore be a template for an unstable transcription complex subject to stochastic regulation, allowing an oscillatory transcriptional response to physiological signals. This suggests that precise timing and coordination of cell responses to different signal-duration may represent a novel mechanism for coordinating long-term dynamic changes in transcription in cell populations.

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