Endocrine Abstracts

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...

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...

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 ...

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...

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...

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...

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.</...

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...

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...