Endocrine Abstracts

Pituitary and adrenal gland assessment, is one of the most important aspects of the management of a pituitary and adrenal adenoma.Clinical practice varies widely with regard to assessment of pituitary and adrenal status pre- and post-operative. Pre-operative testing includes dynamic testing to assess function which is not practical in the immediate post-operative period. Instead a single morning serum total hormones are measured while a more definitive a...

Actions of the stress hormone, glucocorticoid (GC), are essential for the modulation of implicated biological processes such as synaptic transmission. In disease paradigms that feature a hormone hyper-secretion phenotype (e.g. neurocognitive disorders), the normalcy of receptor signaling is compromised.The pro-cognate role of Glucocorticoid receptor (GR) inhibition via hormone analogues bearing anti-glucocorticoid properties is well described. A key exam...

Background: Hormones oscillate in circadian and ultradian rhythms. Single time point samples are difficult to interpret and high frequency measurements are time consuming, expensive and invasive. We developed a minimally invasive technique of ambulatory, automated microdialysis. This allows frequent 24-hour sampling of interstitial fluid while participants continue normal daily activities.Methods: Healthy volunteers (age 18–68, no regular medication...

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...

ACTH signalling at the adrenal zona fasciculata induces rapid synthesis of glucocorticoids, accompanied by rapid transcription of genes encoding steroidogenic enzymes, including the labile, rate-limiting protein, StAR protein. ACTH induction of StAR transcription has been demonstrated to be predominantly CREB-dependent, and this mechanism is regulated by both CREB phosphorylation and its binding to the CREB co-activator TORC (transducer of regulated CREB activity, also known a...

In order to understand the significance of circadian and ultradian hormonal rhythms in man, both in health and disease, it is essential to be able to obtain multiple samples over extended periods, especially during the hours of sleep. The human automated blood sampling (HABS) system reported by Henley and colleagues can achieve this but is recommended for use in the setting of a clinical investigation unit which is its major drawback. For many diagnostic and scientific questio...

Rhythms and change are fundamental properties of all living things, having evolved to allow adaptation to life on earth. Rhythmicity can be observed both in behaviour and internal biology of all mammals including humans. Hormonal secretion patterns that occur at circadian and or ultradian frequencies occur commonly in the endocrine system but for practical and pragmatic reasons clinicians tend to sample and attempt to interpret single time point measures. These results can oft...

Background: Establishing endocrine diagnoses including pituitary Cushing’s remains challenging with delayed or misdiagnosis being very costly for both patient and the health care system. A key issue is that standard diagnostic tests are typically single time point, single analyte samples, which do not consider dynamic variation intrinsic to endocrine systems. Having previously demonstrated that free tissue hormones correlate strongly with plasma concentrations, we present...

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...