Endocrine Abstracts

Fibroblasts are important regulators of local inflammatory responses. These responses are further regulated by tissue glucocorticoid levels. Other stromal lineage cells, adipocytes and osteoblasts, express 11beta-hydroxysteroid dehydrogenases (11b-HSDs) which interconvert inactive cortisone and active cortisol. These enzymes are important regulators of local glucocorticoid levels and their expression is regulated by proinflammatory cytokines. We therefore examined expression o...

Critical illness due to sepsis, trauma, surgery, organ failure or burns is associated with dramatic effects on most hormonal axes. Complex changes occur at the hypothalamic, pituitary, circulatory and tissue levels of hormone action. In the early stages of critical illness these changes appear to be adaptive but this may not be the case in prolonged illness. Common problems faced by endocrinologists are the recognition of pre-existing endocrine disorders in critically ill pati...

Glucocorticoids have potent but paradoxical effects on bone. In vitro they are required for the differentiation of osteoblasts but in excess can cause suppression of the mature osteoblast phenotype by reducing proliferation and inducing apoptosis. In vivo, glucocorticoids are anabolic at physiological concentrations, but in excess have an adverse effect on the skeleton most clearly seen in steroid-induced osteoporosis. We have postulated that this paradox may be ...

Background: The adverse effects of corticosteroid therapy are similar to those of endogenous glucocorticoid excess. Previous studies have established the usage patterns of oral corticosteroids in the primary healthcare setting, but these have concentrated on corticosteroid-induced osteoporosis. The aim of this study was to investigate the prevalence and morbidity of long-term oral corticosteroids in a General Practice setting.Methods: From a population ...

Harvey Cushing’s work informed us of the deleterious consequences of circulating cortisol excess – hypertension, osteoporosis and obesity that contributes to diabetes and premature mortality. Conversely, Hench, Kendall and Reichstein were Nobel Laureates in Physiology 1950 for the discovery of cortisone and demonstrating efficacy in patients with Rheumatoid Arthritis – in effect the birth of the anti-inflammatory actions of glucocorticoids.<p class="abstext"...

The risk of bone fracture at most skeletal sites rises rapidly with age. Changes in bone mass account for only a small part of this increased risk - an additional factor is the progressive reduction in the ability to form new bone. This decrease in bone formation and increased fracture risk is reminiscent of changes seen with glucocorticoid excess, however, circulating corticosteroid levels do not change with age. We have proposed that local rather than circulating levels of c...

Osteosarcoma (OS) is an aggressive malignant tumour of osteoblasts occurring predominantly in children and young adults. Despite chemotherapy relapse is common and mortality remains ~50%. Non-transformed osteoblasts are highly sensitive to glucocorticoids which reduce proliferation and induce apoptosis. Previously, we observed that OS cells, but not normal osteoblasts, express 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme powerfully inactivates cortis...

When used to treat inflammatory disease therapeutic glucocorticoids (GCs) cause rapid bone loss. However clinical studies suggest that in patients without inflammation GCs have little impact on the skeleton. The mechanism by which inflammation magnifies the effects of GCs is unknown. We have proposed that intracellular GC generation (inactive cortisone/prednisone to active cortisol/prednisolone conversion) via the 11 beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) enzyme d...

Acute inflammation plays an important role in the normal immune system by helping to coordinate host responses to danger signals such as infection. In most cases the inflammation is rapidly resolved but in chronic inflammatory diseases such as rheumatoid arthritis (RA) the inflammation persists leading to localized accumulation of potentially damaging immune cells. It remains unclear why inflammation persists in some tissues and not in others. Recent studies have shown that st...

Glucocorticoids (GCs) are important therapeutic agents for a wide-variety of inflammatory diseases but are known to have potentially detrimental side-effects such as osteoporotic bone-loss. These effects of GCs are mediated via the intracellular GC receptor (GR) and by local GC metabolism catalyzed by 11beta-hydroxysteroid dehydrogenase (11beta-HSD). We have postulated that autocrine activation of GCs via 11beta-HSD1 plays a key role in counteracting the effects of inflammator...