This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Friedrichsen, S. Articles by Davis, J. R. E. Search for Related Content PubMed PubMed Citation Articles by Friedrichsen, S. Articles by Davis, J. R. E.

Tumor Necrosis Factor- Activates the Human Prolactin Gene Promoter via Nuclear Factor-B Signaling

Endocrine Science Research Group (S.F., M.W., A.D.A., J.R.E.D.), University of Manchester, Manchester M13 9PT, United Kingdom; Centre for Cell Imaging (C.V.H., D.G.S., G.N., M.R.H.W.), School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom; and Molecular Physiology Group (S.S., J.J.M.), University of Edinburgh Medical School, Edinburgh EH16 4TJ, Scotland, United Kingdom

Address all correspondence and requests for reprints to: Prof. Julian Davis, Endocrine Science Research Group School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom. E-mail: julian.davis{at}manchester.ac.uk; or Prof. Michael White, School of Biological Sciences, Centre for Cell Imaging, University of Liverpool, Liverpool L69 7ZB, United Kingdom. E-mail: m.white{at}liverpool.ac.uk.

Pituitary function has been shown to be regulated by an increasing number of intrapituitary factors, including cytokines. Here we show that the important cytokine TNF- activates prolactin gene transcription in pituitary GH3 cells stably expressing luciferase under control of 5 kb of the human prolactin promoter. Similar regulation of the endogenous rat prolactin gene by TNF- in GH3 cells was confirmed using real-time PCR. Luminescence microscopy revealed heterogeneous dynamic response patterns of promoter activity in individual cells. In GH3 cells treated with TNF-, Western blot analysis showed rapid inhibitory protein B (IB) degradation and phosphorylation of p65. Confocal microscopy of cells expressing fluorescence-labeled p65 and IB fusion proteins showed transient cytoplasmic-nuclear translocation and subsequent oscillations in p65 localization and confirmed IB degradation. This was associated with increased nuclear factor B (NF-B)-mediated transcription from an NF-B-responsive luciferase reporter construct. Disruption of NF-B signaling by expression of dominant-negative variants of IB kinases or truncated IB abolished TNF- activation of the prolactin promoter, suggesting that this effect was mediated by NF-B. TNF- signaling was found to interact with other endocrine signals to regulate prolactin gene expression and is likely to be a major paracrine modulator of lactotroph function.

This article has been cited by other articles:

				A. D. Adamson, S. Friedrichsen, S. Semprini, C. V. Harper, J. J. Mullins, M. R. H. White, and J. R. E. Davis Human Prolactin Gene Promoter Regulation by Estrogen: Convergence with Tumor Necrosis Factor-{alpha} Signaling Endocrinology, February 1, 2008; 149(2): 687 - 694. [Abstract] [Full Text] [PDF]