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Dynamic Patterns of Growth Hormone Gene Transcription in Individual Living Pituitary Cells

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

Address all correspondence and requests for reprints to: Dr. 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 Professor J. R. E. Davis, Endocrine Sciences Research Group, School of Medicine, University of Manchester, Stopford Building, Manchester M13 9PT, United Kingdom. E-mail: julian.davis{at}man.ac.uk.

Real-time imaging of the GH gene promoter linked to luciferase in living pituitary cells has revealed surprising heterogeneity and variety of dynamic patterns of gene expression. Cells treated with either forskolin or thyroid hormone generated a consistent and characteristic temporal response from cell populations, but detailed analysis of individual cells revealed different patterns. Approximately 25–26% of cells displayed no response, 25–33% of cells exhibited a sustained progressive rise in luciferase activity, and 41–50% showed a transient phasic, or oscillatory response, after given stimuli. In cells treated consecutively with the two stimuli, the population response to the second stimulus was augmented. Single-cell analysis revealed that this was partly due to an increased number of cells responding, but also that the prevalence of response patterns changed: cells that responded to an initial stimulus were more likely to respond subsequently in a progressive sustained manner. In conclusion, these studies have indicated that GH promoter activity in individual living pituitary cells is unstable and possibly stochastic, with dynamic variations from hour to hour. The prevalence of different temporal patterns of response to hormonal stimulation among a population of cells is altered by the endocrine history of those cells.

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