Endocrine Abstracts

Biological systems are invariably dynamic, with both stochastic interactions and deterministic processes across multiple timescales ensuring the maintenance of homeostatic regulation and allowing us to adapt to changes in both internal and external environments. It is no surprise therefore that the stress responsive hypothalamic-pituitary-adrenal (HPA) axis shows multiple levels of regulation which come together to regulate oscillating levels of glucocorticoid secretion with b...

The circadian variation of hypothalamo-pituitary-adrenal (HPA) activity is well recognised, with levels of glucocorticoid rising in anticipation of the activity of the coming day (in humans) or night (in rodents). Less well recognised however, is that in common with many other hormones, both ACTH and corticosteroids are released in a pulsatile pattern – with the largest pulses occurring in the morning in man – explaining the large range of ‘normal’ morning ...

Stafford Lightman is Professor of Medicine at the University of Bristol and is Director of the Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology. He started his scientific career working on catecholamines and opioid peptides with Leslie Iversen at the University of Cambridge and provided some of the first data linking opioid peptides with the regulation of neurohypophysial function. At this time he also performed some of the first studies demonstrating...

The HPA axis has a massive dynamic response rate. At nadir periods (at night in man and during the day in nocturnal rodents) there is a low level of activity which increases up until the circadian peak. This circadian rhythm is made up of an underlying ultradian rhythm of pulsatile glucocorticoid section, with pulse amplitude increasing from the circadian nadir to the circadian peak. Superimposed on this underlying rhythm is, of course, the stress response which can result in ...

Glucocorticoid hormones (cortisol in man, corticosterone in rodent; CORT) are vital for maintaining normal homeostasis in multiple systems ((e.g., the cardiovascular, metabolic, and immune systems), and for an optimal response to acute and chronic stress. Plasma CORT is released from the adrenal zona fasciculata (ZF) in response to circulating levels of pituitary-derived adrenocorticotropin hormone (ACTH). ACTH binds to the MC2-receptor on the membra...

Glucocorticoid hormones (cortisol in man, corticosterone in rodent; CORT) are vital for maintaining normal homeostasis in multiple systems ((e.g., the cardiovascular, metabolic, and immune systems), and for an optimal response to acute and chronic stress. Plasma CORT is released from the adrenal zona fasciculata (ZF) in response to circulating levels of pituitary-derived adrenocorticotropin hormone (ACTH). ACTH binds to the MC2-receptor on the membra...

Pharmacological treatment with synthetic glucocorticoids, which are widely prescribed for the treatment of numerous inflammatory and autoimmune diseases, can also affect the way the adrenal gland produces cortisol. Indeed, patients undergoing synthetic glucocorticoid treatment can develop adrenal insufficiency. This condition is characterised by reduced responsiveness of the adrenal to ACTH stimulation, and adrenal crisis/shock can occur in response to acute physiological stre...

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...

Background and case: A 38-year-old man presented acutely with left-sided retro-orbital pain, a heavy/numb sensation in his left arm and blurred vision and diplopia on left lateral gaze. Baseline biochemistry, liver function and haematology were normal. His TSH was 3.9 (0.3–4 mU/l) and CRP 92 mg/l (<10). Plain CT head was unremarkable as was the MRI as reported, and atypical migraine was suspected. Vertical diplopia on left lateral gaze and left upper arm paraesthesia ...

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...