Endocrine Abstracts

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...

Synthetic peroxisome proliferator-activated receptor gamma (PPARγ) ligands are used clinically to improve insulin sensitivity. Although designed as specific ligands for PPARγ, there is evidence for some ‘off target’ effects being mediated by a non-classical, non-PPARγ mechanism. Recent evidence further suggests that some of these effects may be glucocorticoid receptor (GR)-dependent.To analyse activation of GR following exposure ...

Thyroid eye disease is the most frequent extrathyroidal manifestation of Graves’ disease. Severe and active disease is frequently treated with immunosuppressive therapy. IV methylprednisolone (500 mg daily for 3 days) is the treatment of choice with efficacy rates of up to 77%. New onset glucose intolerance/diabetes is the most relevant side effect of this treatment. We investigated the risk of steroid induced diabetes and the risk factors for its development.<p class...

Glucocorticoids (Gcs) are important regulators of cellular homeostasis, with their effects mediated by the intracellular glucocorticoid receptor (GR). Once activated, the GR may initiate rapid effects within the cytoplasm, but also translocate to the nucleus to affect gene transcription. The subcellular localisation of the GR is therefore an important determinant in the cellular response to Gcs.To analyse subcellular trafficking of the GR, HeLa cells wer...

Glucocorticoids (Gc) act through the glucocorticoid receptor (GR) to regulate gene transcription, but also initiate a number of rapid non-genomic effects. The inactive GR is found complexed with hsp90 and immunophilins. Several other signalling molecules including c-src and raf-1 also associate with hsp90. Evidence suggests that Gc treatment results in the rapid activation and dissociation of GR and c-src from these complexes. We speculate that GR-mediated activation of one or...

Background: Over 90% of the blood supply to the adenohypophysis arises from hypothalamic portal vessels, in contrast to the systemic blood supply to the posterior lobe. A pre-existing, or tumour stimulated direct (non-portal) blood supply has been suggested as a possible pathogenic mechanism for prolactinoma development.Methods: 6 patients (3 microprolactinomas (mic), and 3 macroprolactinomas (mac)), and one control subject were imaged using a 3T magnet...

Glucocorticoids (Gc) act through the glucocorticoid receptor (GR) to regulate immunity, energy metabolism, and tissue repair. The inactive GR is held in the cytoplasm in a multi-protein complex, which upon ligand binding undergoes a conformational change. Activated GR translocates to the nucleus to regulate gene expression (over hours), but some effects occur more rapidly. Gc inhibit cell migration through an uncertain mechanism. We now show a very rapid effect, and surprising...

Glucocorticoids (Gc) act through the glucocorticoid receptor (GR) to regulate immunity, energy metabolism, and tissue repair. The inactive GR is held in the cytoplasm in a multi-protein complex, which upon ligand binding undergoes a conformational change. Activated GR translocates to the nucleus to regulate gene expression (over hours), but some effects occur more rapidly. Gc inhibit cell migration through an uncertain mechanism. We now show a very rapid effect, and surprising...

Glucocorticoids (Gc) are potent anti-inflammatory steroids which mediate their effects by binding the glucocorticoid receptor (GR). Following ligand binding, GR initiates rapid ‘non-genomic’ kinase signals in the cytoplasm, then translocates into the nucleus to mediate ‘genomic’ effects by binding DNA directly or tethering to other DNA bound transcription factors to modulate target gene expression. Little is known about how rapidly induced cytoplasm derived...

Glioblastoma (GBM) is a highly aggressive form of brain cancer with a median survival time of 12–15 months from diagnosis. Standard therapies utilise a combination of radiotherapy, chemotherapy, and surgery. Patients also receive high doses of the potent anti-inflammatory glucocorticoid (Gc), Dexamethasone (Dex).Recent studies show that patients receiving the highest dose of Dex also have reduced survival time. Defining pathways under Gc control relevant to GBM is necessa...