Endocrine Abstracts

Ultradian rhythms of glucocorticoid hormones is crucial for optimal glucocorticoid-target gene expression, and therefore it is important to understand the mechanisms regulating glucocorticoid pulsatility and how it becomes disrupted in disease. I will discuss our recent findings on how the adrenal steroidogenic pathway responds dynamically to pulses of ACTH, both in vitro in adrenocortical cells and in vivo in the rat, and how these dynamics become disrupted ...

The activity of the hypothalamic–pituitary–adrenal (HPA) axis is characterized by an ultradian (pulsatile) pattern of glucocorticoid secretion that is critical for optimal transcriptional, neuroendocrine and behavioural responses to glucocorticoids. We have investigated the molecular mechanisms underlying the origin of glucocorticoid ultradian rhythm within the rat adrenal gland. We show that this rhythm of glucocorticoids depends on highly dynamic processes within a...

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...

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...

The hypothalamic-pituitary-adrenal axis is the primary neuroendocrine system activated to establish homeostasis during the stress of critical illness and surgery. However, such critical states also trigger a systemic inflammatory activation that usually precedes the release of adrenocorticotrophic hormone (ACTH) and cortisol. Systemically or locally induced inflammation of the adrenal gland had been described during critical illness. This facilitates...

The hypothalamic-pituitary-adrenal axis is the primary neuroendocrine system activated to establish homeostasis during the stress of critical illness and surgery. However, such critical states also trigger a systemic inflammatory activation that usually precedes the release of adrenocorticotrophic hormone (ACTH) and cortisol. Systemically or locally induced inflammation of the adrenal gland had been described during critical illness. This facilitates...

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...

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...