Endocrine Abstracts

Chronic elevation of plasma glucocorticoids adversely affects cognitive processes and the structural and functional integrity of the hippocampus. Crucially, inter-individual differences in memory with ageing directly associate with blood glucocorticoid levels in rodents and humans; indeed higher plasma corticosterone in mid-life in rodents predict subsequent memory impairments. However, although keeping glucocorticoid levels low by adrenalectomy in adult life prevents the emer...

Numerous epidemiological studies worldwide have shown a strong association between low birth weight and an increased risk of developing cardiometabolic disease, including hypertension. Excessive fetal exposure to glucocorticoids has been hypothesised to mediate this relationship. Here, we have used an established rodent model – in which dexamethasone, a synthetic glucocorticoid that readily crosses the placenta, is administered to pregnant Wistar rats during the last trim...

Various psychiatric conditions have been associated with stress and alterations in hypothalamic-pituitary-adrenal (HPA) activity. Yet while stress is a general phenomenon, illness is only seen in a proportion of individuals, suggesting genetic modifiers of ability to cope with stress. 11-beta hydroxysteroid dehydrogenase type 1 (HSD1) regenerates corticosterone from inert 11-dehydrocorticosterone, amplifying the levels of glucocorticoids and is expressed in the brain. To deter...

Although the anti-inflammatory effects of exogenous glucocorticoids (GC) upon inflammation are well recognized, the contribution of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), an amplifier of GC action in vivo, in modulating endogenous GC action during inflammation is unknown. Mouse models of arthritis and lung inflammation were used to explore the role of 11β-HSD1 in acute and chronic inflammation. Arthritis was induced in 11β-HSD1−/&#...

Inactivating mutations of the POMC gene in humans and mice result in a complex phenotype of hyperphagia, obesity and glucocorticoid (GC) deficiency, but without many features of metabolic syndrome. We have previously shown that replacement of GC in Pomc−/− mice exacerbates their hyperphagia, increases fat mass and elevates plasma leptin and insulin. We have now examined key determinants of glucocorticoid action, including glucocorticoid receptor (...

Obesity/Metabolic syndrome (insulin resistance, hypertension, cardiovascular disease) has reached epidemic levels in western societies. Aberrantly elevated glucocorticoid amplification by intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) within adipose tissue might explain the striking similarities between idiopathic obesity/metabolic syndrome and Cushing’s syndrome, causes by plasma GC excess. A major contributor to obesity/metabol...