Endocrine Abstracts

The detrimental effect of excessive obesity on insulin resistance is well established. The expansion of adipose tissue is dependent on two processes: adipogenesis and angiogenesis and the Wnt signalling pathway has been reported to affect both. In adipose tissue the Wnt signalling pathway functions in a converse manner: increasing commitment of mesenchymal stem cells to preadipocytes and inhibiting differentiation of preadipocytes to mature adipocytes by decreasing expression ...

Glucocorticoid (GC) excess adversely affects many aspects of skin homeostasis, characteristics of which are also seen during ageing (e.g. poor wound healing). The mechanisms underlying this remain unclear. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol, independently of circulating concentrations, and we have previously demonstrated increased 11β-HSD1 expression in human dermal fibroblasts (HDF) from aged donors. We have now e...

In the endo/sarcoplasmic reticulum (ER/SR), hexose-6-phosphate dehydrogenase (H6PDH) generates an NADPH/ NADP ratio sufficient to drive 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-mediated glucocorticoid (GC) activation (11-DHC to corticosterone). In H6PDH knockout (H6PDKO) mice a reduced NADPH/NADP ratio leads to reversed 11β-HSD1 activity (corticosterone to 11-DHC), and GC insensitivity. They also display skeletal myopathy driven by activation of the un...

Male hypogonadism is characterised by sexual dysfunction, loss of muscle bulk, central obesity, fatigue, mood and sleep disturbances, osteoporosis and anaemia. Although these features are associated with low serum testosterone concentration, not all men with a low serum testosterone are definitively hypogonadal, and there is a large symptom overlap with obesity and non-endocrine illness. Importantly, testosterone replacement therapy may not be appropriate for men with mild, fu...

The potent effects of glucocorticoids (GCs) upon carbohydrate metabolism are well described. However, their actions upon lipid metabolism are poorly characterized. Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. The A-ring reductases (5α-reductase type 1 [5αR1] and type 2 [5αR2]), inactivate cortisol as well as generate dihydrotestosterone (DHT) from testosterone (T) and a...

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"...

Nearly all the functions of the liver display zonation in distribution within each the lobule. Hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1). Dysregulation of hepatic 11β-HSD1 activity has been implicated in insulin resistance. Key processes such as gluconeogenesis are located in the periportal hepatocytes, although current dogma describes hepatic 11&#94...

Background: Premature infants are at risk of delayed screening for congenital hypothyroidism (CH), which may markedly affect initial treatment time and neurodevelopmental outcome. Rescreening preterm infants at four weeks (30 days) of life has been recommended to detect cases with delayed TSH elevation.Aim: To examine the performance of the CH screening programme in preterm infants aged ≤32 weeks in terms of timing of the initial Guthrie tests, and...

A 19-year-old student was referred with a history of increasing anxiety attacks, palpitations and breathlessness. Blood pressure and urinary catecholamine levels were elevated. MRI imaging confirmed a para-aortic paraganglionoma and MIBG scan highlighted bony metastases. The patient underwent surgery for the primary lesion and targeted MIBG therapy for metastases.Age of onset, malignant disease and metastases increase the likelihood of a genetic cause an...

Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Although there is a strong inverse correlation between intramuscular triglyceride (IMTG) levels and insulin sensitivity, the impact of glucocorticoids upon the processes that regulate skeletal muscle lipid metabolism has not been explored.Mouse C2C12 skeletal myocytes were grown to confluence and differentiated into myotubes in chemically defined medi...