Endocrine Abstracts

Glucocorticoids (Gc) are potent anti-inflammatory agents, but their clinical use is limited by their significant side effects. The effects of glucocorticoids are mediated by the cytosolic glucocorticoid receptor (GR), which regulates transcription by transactivation or transrepression. Independent of these genomic effects of the GR are other, very rapid non-genomic effects.The glucocorticoid receptor forms a complex with hsp90, FKBP51, FKBP52 and cyp40 i...

The glucocorticoid receptor antagonist, RU486, binds to the glucocorticoid receptor (GR) with high affinity, and allows both nuclear localisation and also DNA binding. However, the DNA bound GR does not activate target gene transcription. This suggests that the ligand-binding domain of the GR is required to interpret agonist and antagonist ligands, and transmit those signals to the basal transcriptional machinery. Adaptor proteins play an important role in transducing the effe...

Glucocorticoids (Gc) are highly potent anti-inflammatory agents. They act through the glucocorticoid receptor (GR), a protein capable of multiple protein interactions. The pro-inflammatory cytokines, TNF-a and IL-1 signal, in part, through activation of NF-kB. Nf-kB transactivation is inhibited by activated GR. It has been suggested that the GR, and the p65 (RelA) component of NF-kB form a direct contact independent of Gc ligand, and that Gc binding results in inhibition of p6...

Coeliac disease is more common in people who have Type 1 diabetes mellitus (DM) because of their autoimmune co-existence. Between 4 and 9% of people with Type 1 DM will also have coeliac disease. The updated NICE guideline (NG 20 coeliac screening) recommends that adult with Type 1 DM should be tested for coeliac disease at diagnosis and retested if any symptoms of coeliac disease develop.Study method & Result: Newly...

Coeliac disease is more common in people who have Type 1 diabetes mellitus (DM) because of their autoimmune co-existence. Between 4 and 9% of people with Type 1 DM will also have coeliac disease. The updated NICE guideline (NG 20 coeliac screening) recommends that adult with Type 1 DM should be tested for coeliac disease at diagnosis and retested if any symptoms of coeliac disease develop.Study method & Result: Newly...

The circadian clock is a key regulator of immune responses. Both circulating and resident immune cells possess intrinsic timers, which act to impart time-of-day variation in their function. It is now becoming evident that the circadian clock is also critically involved in regulating the function of endogenous anti-inflammatory glucocorticoid hormones. Consequently, we see variation in an animal’s inflammatory responses dependent on the time the stimulus was delivered. Thi...

The metastasis related methyltransferase 1 (Merm1), originally designated WBSCR22, is implicated in cancer through H3K9 methylation and silencing of the tumour-suppressor Zac1 gene. Activated GR is a transcription factor with chromatin remodelling activity, and so the functional interaction between GR, and Merm1 was determined. Merm1 consistently potentiated GR transactivation of TAT3-Luc in HeLa cells. This was dependent on the SAM and methyltransferase domains of Merm1. Merm...

Objective: Acclimatization to high-altitude is a dynamic process affecting the neuro-endocrine and physiological systems. Psychological well-being is also influenced by hypobaric-hypoxia. Psychic stress is known to influence the hypothalamo–pituitary–adrenal/thyroid axis. However, the involvement/contribution of ‘psychological-performance’ on hormone changes at high-altitude is not known. The objective of this study was to examine: i) the effect of ethnicit...

Aim: To study those factors which influence the sensitivity and positive predictive value of combined MIBI scintigraphy and ultrasound scan in the localisation of parathyroid adenomas.Method: A retrospective review of notes was done of 150 patients with hypercalcaemia referred to the Endocrine outpatients’ clinic, between the years 2002–2005.Notes of 135 patients with biochemical evidence of primary hyperparathyroidism (P...

Glucocorticoids (GCs) are potent anti-inflammatory agents, but a variable therapeutic response occurs. We have used microarray analysis to explore the basis for inter-individual differences in the GC sensitivity of a healthy volunteer population, and identified genes predictive of response to GCs. Three such discriminating genes were then selected to be investigated for their potential to interact with the Glucocorticoid Receptor (GR). These are the Bone Morphogenetic Protein ...