Endocrine Abstracts

Glucocorticoids are known to have a role in the programming of appetite regulation but the mechanisms have not been fully delineated. This study examined the effect of maternal undernutrition on glucocorticoid receptor (GR) as a key regulator of the appetite regulating neuropeptides, proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the hypothalamus.Ewes were undernourished (UN, n=4) for 30 days pre- and 60 days post-mating or given normal fe...

Maternal undernutrition influences the development of diseases such as obesity and diabetes in the adult offspring. Programming of key genes involved in hypothalamic appetite regulation such as proopiomelanocortin (POMC) and neuropeptide Y (NPY) may affect energy balance in adulthood. These changes may occur by alterations in gene expression or epigenetic changes including histone acetylation and DNA methylation. This study aims to examine the effects of maternal undernutritio...

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...

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.</...

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 ...

Aim: Population studies have shown that basal calcitonin concentrations are below 10 ng/l in the normal population. Ten nanograms per liter is used as a diagnostic cut-off by most laboratories and patients with levels higher than this are offered a pentagastrin stimulation test to exclude medullary thyroid carcinoma. However, these guidelines were adopted from studies that used the Cisbio Immunoradiometric assay for measuring calcitonin. Most laboratories have now moved to che...

Glucocorticoids (Gcs) act via the intracellular glucocorticoid receptor (GR) to regulate cellular homeostasis. GR is a ligand-activated transcription factor which mediates effects within the nucleus or cytoplasm to regulate genomic or 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 in cells transfected with fluorophore-t...

We have previously shown that the ACTH precursor, POMC, is present in human plasma and is the predominant secreted POMC peptide. This suggests that POMC processing is incomplete in neuroendocrine cells and regulation of the post-translational cleavage pathway is important in controlling secretion of ACTH. We have therefore analysed the dynamics of POMC processing in both AtT20 pituitary adenoma cells and primary rat pituitary cells. In both cases, large quantities of POMC, as ...

Aldosterone is key in the development of hypertension. We have shown that a SNP (−344T) in the 5’ regulatory region (UTR) of the gene encoding aldosterone synthase (CYP11B2) was associated with aldosterone excess and high blood pressure. However, the most robust phenotype is altered adrenal 11-hydroxylation efficiency (deoxycortisol to cortisol); a step carried out by 11β-hydroxylase, encoded by the adjacent gene, CYP11B1. We proposed that the effects of CYP11B...

Relaxin-3 is a newly discovered member of the insulin superfamily. It is expressed in the nucleus incertus (NI) of the brainstem which has projections to the hypothalamus. Relaxin-3 binds with high affinity to the G-protein-coupled receptors RXFP1 and RXFP3. RXFP3 is expressed predominantly in the CNS, and in particular within the hypothalamic paraventricular nucleus (PVN). The physiological function of relaxin-3 is unknown but recent work suggests it may play a role in appeti...