Browse by author
Lookup NU author(s): Dr Glyn NelsonORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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-alpha 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-alpha 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-alpha, Western blot analysis showed rapid inhibitory protein kappa B (I kappa B alpha) degradation and phosphorylation of p65. Confocal microscopy of cells expressing fluorescence-labeled p65 and I kappa B alpha fusion proteins showed transient cytoplasmic-nuclear translocation and subsequent oscillations in p65 localization and confirmed I kappa B alpha degradation. This was associated with increased nuclear factor kappa B (NF-kappa B)-mediated transcription from an NF-kappa B-responsive luciferase reporter construct. Disruption of NF-kappa B signaling by expression of dominant-negative variants of I kappa B kinases or truncated I kappa B alpha abolished TNF-alpha activation of the prolactin promoter, suggesting that this effect was mediated by NF-kappa B. TNF-alpha 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.
Author(s): Friedrichsen S, Harper CV, Semprini S, Wilding M, Adamson AD, Spiller DG, Nelson G, Mullins JJ, White MRH, Davis JRE
Publication type: Article
Publication status: Published
Journal: Endocrinology
Year: 2006
Volume: 147
Issue: 2
Pages: 773-781
Print publication date: 01/02/2006
ISSN (print): 0013-7227
ISSN (electronic): 1945-7170
Publisher: The Endocrine Society
URL: http://dx.doi.org/10.1210/en.2005-0967
DOI: 10.1210/en.2005-0967
Notes: 005NN Times Cited:4 Cited References Count:57
Altmetrics provided by Altmetric