Endocrine Abstracts

Dexamethasone (DEX) is a widely used synthetic glucocorticoid whose effects are mediated via glucocorticoid receptor (GRs). Synthetic glucocorticoids are widely used in the clinical setting, due to their potent anti-inflammatory actions. However they are associated with numerous systemic side-effects and may also promote cognitive dysfunction, including impaired memory and learning processes in both patients and animal models.Discrete pulses of endogenou...

Two-way interactions between the hypothalamo–pituitary–adrenal (HPA) axis and the hypothalamo–pituitary–testicular (HPT) axis are well recognised. For example, in rats disruption of the HPT axis alters the circadian secretion of corticosterone. Conversely, stress conditions have varying effects on the level of testosterone secretion in both rats and humans. In contrast to humans, where several pulses of testosterone secretion can be detected across the 24 h...

Endogenous glucocorticoids are secreted in hourly pulses, establishing a characteristic ultradian rhythm. Accordingly, the glucocorticoid receptor (GR) is activated in distinct pulses, causing target-gene pulsing. In contrast, constant glucocorticoid treatment causes aberrant target-gene overexpression in cell culture models, however this has not yet been described in vivo. Therefore, here we assess the effect of altering the glucocorticoid ultradian pattern on transc...

Chronic treatment with the synthetic glucocorticoid (GC) prednisolone has been reported in association with many detrimental health effects. In addition to well-documented adverse metabolic effects, there is evidence for memory impairments in these patients. GCs are known to have effects on memory, either enhancing or impairing dependant upon timing of exposure. Cell experiments have shown that synthetic GCs such as methyl-prednisolone (MPL) cause an alteration in timing of gl...

Ultradian glucocorticoid (GC) secretion is highly conserved, having been detected in all species studied. The GC corticosterone (CORT) is a ligand for the glucocorticoid receptor (GR), inducing GR recruitment to glucocorticoid responsive elements (GREs) to modulate transcription of GC-target genes. We have previously demonstrated that pulsatile GR recruitment to GREs upstream of the Period1 gene is associated with its pulsatile transcription in rat liver. Similarly th...

Glucocorticoids act via the glucocorticoid receptor (GR). Upon ligand binding, GR translocates to the nucleus and binds directly to glucocorticoid responsive elements (GREs) to regulate transcriptional output. Glucocorticoid secretion increases in response to stress to affect transcriptional output within specific areas of the brain including the hippocampus (HC). Therefore, here we assess changes in genome-wide GR chromatin binding profiles in the rat HC in response to a gluc...