Searchable abstracts of presentations at key conferences in endocrinology

ea0009p125 | Endocrine tumours and neoplasia | BES2005

Oestrogen interacts with TNFalpha signalling pathways to stimulate human prolactin gene transcription

Adamson A , Friedrichsen S , Wilding M , White M , Davis J

Oestrogen is an important regulator of the pituitary hormone prolactin (PRL) in vivo, although the regulation mechanism is poorly understood. Liganded oestrogen receptor (ER) synergises with the pituitary specific factor Pit-1 on the rat PRL promoter to facilitate chromatin looping and increased transcription; however, no such mechanism has been reported for the human PRL promoter, in which the ERE sequence is altered.In pituitary GH3 cells stably transf...

ea0019p332 | Steroids | SFEBES2009

Mitosis regulates GR trafficking and impacts GR function

Matthews L , Spiller D , Rivers C , Norman M , White M , Ray D

Glucocorticoids (Gcs) act via the intracellular glucocorticoid receptor (GR) to regulate cellular homeostasis. GR is a ligand-activated transcription factor that mediates effects within the nucleus or cytoplasm to regulate genomic and non-genomic events. Localisation of the GR to a specific cellular compartment is therefore an important determinant of the cellular response to Gcs.Live cell imaging of GR trafficking using fluorophore-tagged GR shows drama...

ea0019p334 | Steroids | SFEBES2009

GR is hyperphosphorylated during mitosis and associates with the mitotic spindle

Matthews L , Spiller D , Rivers C , Norman M , White M , Ray D

Glucocorticoids (Gcs) act via the intracellular glucocorticoid receptor (GR) to regulate cellular homeostasis. Previous studies have demonstrated altered Gc sensitivity during mitosis. This reduced sensitivity can be explained only in part through the selective export of GR in mitotic cell populations. In this study ligand-independent, cell cycle-dependent effects on GR have been explored.Mitotic cells show a marked increase in ligand-independent ser211 ...

ea0021sb1.2 | How to access funds and revolutionise your research | SFEBES2009

Integration of live cell imaging and mathematical modelling: how to use systems biology to revolutionise your research

White M

The advent of high throughput techniques and genome sequencing has brought about a new era in the availability of biological data. This has created a need for new approached for data integration and to interpret complex biological data sets. A cell cannot be considered as using a set of independent signalling pathways. Instead, it is now clear that signalling proteins are integrated into a complex network. The human brain cannot handle this complexity. At the same time, we nee...

ea0005s24 | Prolactin: Novel Aspects | BES2003

Regulation of prolactin gene expression

Davis J , White M

Prolactin is produced by pituitary lactotrophic cells and by several extrapituitary tissues, including immune cells and the endometrium in man. It has a wide range of actions at different sites, and hyperprolactinaemia and prolactinomas give rise to common clinical problems. The human prolactin gene contains six exons, with two distinct promoters that direct pituitary or extra-pituitary transcription respectively. The pituitary-specific promoter extends over 5000 base-pairs an...

ea0029oc4.2 | Pituitary Basic | ICEECE2012

Transcriptional regulation of prolactin by oestrogen in vivo

Patist A. , Featherstone K. , Spiller D. , Semprini S. , McNeilly J. , McNeilly A. , Mullins J. , White M. , Davis J.

Circulating levels of prolactin are subject to acute and long-term regulation by many factors including oestrogen and dopamine. We have studied the regulation of prolactin promoter activity in living pituitary cells using transgenic Fischer rats in which reporter gene expression is regulated by the human prolactin gene locus (hPRL-d2EGFP). We have previously identified pulsatile prolactin transcription patterns in living lactotroph cells in fetal tissue, that became stabilised...

ea0019p333 | Steroids | SFEBES2009

Altered subcellular trafficking and gene regulation suggest a distinct role for GR gamma

Berry A , Matthews L , Rivers C , Spiller D , White M , Norman M , Ray D

The actions of glucocorticoids (Gc) are mediated by the glucocorticoid receptor (GR). Several isoforms of the GR exist. Whilst GR alpha is the most abundant isoform, constitutive alternative splicing at the exon 3/exon 4 boundary results in an additional arginine within the DNA binding domain to produce the gamma isoform. Although GR gamma comprises 4–8% of total GR transcripts and is highly conserved through mammalian evolution, its biological function remains unknown.</...

ea0009oc20 | Oral Communication 3: Neuroendocrinology | BES2005

Transcriptional activation of the prolactin gene by TNF-alpha is mediated via NFkB

Friedrichsen S , Wilding M , Harper C , Nelson G , Spiller D , White M , Davis J

The neuroendocrine and immune systems are closely linked, and cytokines such as IL-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha), secreted by immune cells or neighbouring pituicytes, may have important local effects on pituitary function to modulate endocrine mechanisms of regulation.We have analysed the transcriptional regulation of the human prolactin (hPRL) gene promoter by TNF-alpha. Using stably transfected GH3 cells expressing luciferase und...

ea0007p41 | Diabetes, metabolism and cardiovascular | BES2004

The N363S polymorphism of the glucocorticoid receptor in South Asians in the North East

Syed A , Irving J , Redfern C , Hall A , Unwin N , White M , Bhopal R , Alberti K , Weaver J

Some people with obesity have hormonal, metabolic and circulatory changes that constitute the metabolic syndrome that resemble characteristics of patients with Cushing's syndrome. A link between the two conditions, possibly genetic, has therefore been suspected, and the glucocorticoid receptor gene (GRL, 5q31-q32) has been one of the candidate genes.The single nucleotide polymorphism N363S is an ATT to GTT missense alteration within exon 2 of G...