Endocrine Abstracts

Human studies indicate that local glucocorticoid (GC) generation within osteoblasts plays a critical role in various bone diseases. Human osteoblasts express the enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) that converts inactive GCs (cortisone, dehydrocorticosterone) to their active counterparts (cortisol, corticosterone). This activation capacity critically depends on expression of a cofactor generating enzyme hexose-6-phosphate dehydrogenase. Enzyme expression ...

A para 2+0 female, 11 weeks gestation presented with vaginal bleeding and hyper-emesis. An ultrasound scan showed a dichorionic pregnancy with one viable foetus and a hydatiform mole. β-human chorionic gonadotrophin (β-hCG) level was elevated at 159845 U/L and subsequent thyroid biochemistry revealed hyperthyroidism. Serum thyrotrophin (TSH) was suppressed at <0.05 mU/L (NR 0.2–4.5), with a FT4 37 pmol/L (NR 9–24), and Free T3 of 17.8 nmol/L (NR 2.6&#15...

Human studies have suggested that local glucocorticoid (GC) generation within osteoblasts plays a critical role in bone loss seen during aging, in response to inflammation and treatment with GCs. Human osteoblasts express the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that converts inactive GCs (cortisone, dehydrocorticosterone, prednisone) to their active counterparts (cortisol, corticosterone, prednisolone). Enzyme expression increases with age, in r...

Tissue inflammation is usually transient but in diseases such as rheumatoid arthritis (RA) inflammation persists. It remains unclear why inflammation persists in some tissues and not in others. Recent studies have shown that stromal cells such as fibroblasts play a pivotal role in determining this persisitance. We have hypothesized that glucocorticoid (GC) activation via the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) within fibroblasts plays a key role in ...

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...

Endocrine disruptors are chemicals which in low concentrations can disturb gene expression in a range of endocrine glands and organs including the fetal and adult adrenal glands, potentially resulting in altered steroidogenic flux. With exposure to endocrine disruptors affecting both animals and humans, it is important to assess both the mechanisms and consequences of disruption in steroidogenic pathways, particularly as foetal development may be especially sensitive to endocr...

Glucocorticoids (GCs) have potent immunomodulatory and anti-inflammatory effects and are widely used in the treatment of inflammatory diseases. Unfortunately, their long term administration causes serious systemic metabolic side effects including osteoporosis, muscle wasting and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is responsible for the local conversion of inactive GCs to their active counterparts. It has been shown that many of the...

Local and systemic bone loss is a common complication in patients with chronic inflammatory disease. Previously, we have identified that glucocorticoid (GC) activation by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is increased within tissues such as bone during systemic inflammation. However, whilst effective at suppressing inflammation, in excess, GCs drive osteoporosis. To determine the contribution of 11β-HSD1 activated glucocorticoids to inf...

Glucocorticoids (GCs) have potent immunomodulatory and anti-inflammatory effects and are widely used in the treatment of inflammatory diseases. Unfortunately, their long term administration causes serious systemic metabolic side effects including osteoporosis, muscle wasting and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is responsible for the local conversion of inactive GCs to their active counterparts. It has been shown that many of the...

Local and systemic bone loss is a common complication in patients with chronic inflammatory disease. Previously, we have identified that glucocorticoid (GC) activation by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is increased within tissues such as bone during systemic inflammation. However, whilst effective at suppressing inflammation, in excess, GCs drive osteoporosis. To determine the contribution of 11β-HSD1 activated glucocorticoids to inf...