Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 21 P299

Pituitary

Immuno-modulatory role of prolactin in immune tissues driven by the alternative promoter

Anne McNamara1, Raheela Awais1, Sabrina Semprini2, Claire Harper1, Karen Featherstone3, Dave Spiller1, Julian Davis3, John Mullins2 & Mike White1


1University of Liverpool, Liverpool, UK; 2University of Edinburgh, Edinburgh, UK; 3University of Manchester, Manchester, UK.


Prolactin (PRL) is a hormone mainly produced by the lactotroph cells of the anterior pituitary gland. Besides its pivotal role in reproduction, PRL has also been found to have immuno-modulatory properties. The pituitary is the main source of circulating PRL, however it is also expressed in humans at extra-pituitary sites1. In extra-pituitary tissues, PRL mRNA contains an extra exon (exon 1a), and expression is regulated by an alternative promoter upstream of the pituitary transcription start site.

Previously, we have generated a transgenic rat that expresses luciferase under the control of entire human PRL gene locus. In vivo bioluminescence imaging of the anaesthetised intact animal following inflammatory stress showed a dramatic induction in luciferase expression in extra-pituitary tissues, in particular the thymus and spleen which was shown to be driven by the alternative PRL promoter1.

In order to further explore the regulation of extra-pituitary PRL gene expression and its association with inflammatory response we carried out an ex-vivo study to assess the effect of a range of inflammatory stimuli on PRL expression in immune-related organs. Dispersed cell preparations from spleen and thymus of PRL-luciferase transgenic rats were treated with stimuli and assayed for luciferase activity. Stimuli included lymphocyte activators, growth factors, cytokines, LPS and oestrogen, all of which either have a potential role in inflammatory stresses or have been shown to regulate PRL expression.

These stimuli were able to induce PRL expression in both male and female splenic and thymic cultures with the greatest induction following LPS treatment (approximately threefold). Induction in luciferase expression was confirmed to be driven by the alternative promoter by RT-PCR. These results support the potential role of PRL as an immune-regulator in addition to its endocrine function and provide basis for further investigations to identify the cell types and pathways involved in inflammatory responses.

Reference

1. Semprini et al. Mol Endo 2009 23 529–538.

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