Endocrine Abstracts

In the clinic, glucocorticoids are widely used due to their anti-inflammatory properties. Despite their huge benefits, prolonged use is often associated with severe side effects as well as the development of glucocorticoid resistance in some cases. Mutations in an important SWI/SNF subunit, ARID1a, have previously been linked to glucocorticoid resistance and are associated with a vast number of human cancers. Determining the functional role of ARID1a...

In the clinic, glucocorticoids are widely used due to their anti-inflammatory properties. Despite their huge benefits, prolonged use is often associated with severe side effects as well as the development of glucocorticoid resistance in some cases. Mutations in an important SWI/SNF subunit, ARID1a, have previously been linked to glucocorticoid resistance and are associated with a vast number of human cancers. Determining the functional role of ARID1a...

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...

AT-rich interacting domain (ARID) subunits can interact with the glucocorticoid receptor (GR) and therefore may be essential for gene transcription dependent on receptor signalling. Glucocorticoids are steroid hormones important for regulating a variety of physiological processes through the binding and activation of GR. GR associates with numerous co-regulators, such as chromatin remodelling factors, to mediate gene induction or repression. One chromatin remodelling complex w...

Clinically, glucocorticoids are widely used as a treatment mainly due to their potent anti-inflammatory abilities, however these are associated with several side effects and furthermore some patients go on to develop glucocorticoid resistance. ARID1a mutations have been linked to glucocorticoid resistance and are frequently identified across numerous cancers; therefore it is important to determine the functional role of ARID1a to GR signalling. The ATPase driven SWItch/Sucrose...

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...