Endocrine Abstracts

Testosterone, androstenedione and DHEAS are commonly measured by immunoassays. Variations in antibody specificity and calibration of assays results in non-commutability of measurements. Even more specific mass spectrometry (LC–MS/MS) assays still exhibit differences in calibration. As the use of mass spectrometry for measuring steroids is becoming more common in the clinical laboratory, the development of LC–MS/MS reference ranges for these analytes is essential to h...

Cofactors of the nuclear hormone receptors are crucial in regulating their transcriptional activity. The glucocorticoid receptor (GR) is a member of the nuclear hormone receptor superfamily, involved in the regulation of metabolism, inflammation and stress–responses and many GR cofactors are known, including p300. Here, we identify a new cofactor for GR: TTC5/Strap, tetratricopeptide repeat domain 5/ stress–responsive activator of p300. Strap is a TPR motif containin...

Although glucocorticoids (Gc) are used to treat a range of pathologies, an individuals response to therapy varies considerably. There is a distinct correlation between certain cell types and steroid sensitivity. Aberrant glucocorticoid receptor (GR) function is well-characterised in lymphoid malignant cells but not small cell lung cancer (SCLC) (DMS79) or osteosarcoma (U2OS) cell lines, which are both Gc resistant.Previously we have shown reduced GR cont...

We report of two sisters with hyperandrogenism, menstrual abnormalities, and severe insulin resistance. The elder sister was seen after puberty at age 21 and she was referred for the evaluation of hirsutism and polymenorrhoea; the younger was seen earlier in life, at age 15, for the evaluation of secondary amenorrhoea. In both of them, we performed the diagnosis of polycystic ovary syndrome (PCOS) in accordance to the Rotterdam criteria. They also presented a lipodystrophic ph...

MIF is a potent pro-inflammatory mediator that opposes the anti-inflammatory actions of glucocorticoids (Gc) and is involved in the pathogenesis of multiple diseases. The MIF promoter is inhibited by Gc in lymphocytes (CEMC7A) but not in epithelial cells (A549), despite expression of functional glucocorticoid receptors (GR) in both. Deletion studies localized the cis element responsible for Gc inhibition to between MIF −71 and +85. This sequence contained no GR binding s...

Glucocorticoid (GC) excess is characterized by central obesity, insulin resistance and in some cases, type 2 diabetes mellitus. Whilst it is accepted that GCs cause insulin resistance, both insulin and GCs act synergistically to promote adipocyte differentiation. We have previously shown that acute treatment (24 h) with GCs enhances insulin signalling in human adipocytes. We hypothesise that the generation of cortisol from inactive cortisone by 11β-hydroxysteroid dehydrog...

Background: Obesity levels and the demand for obesity services are increasing. Those with morbid obesity require specialist care and consideration for bariatric surgery. Based on recent figures and NICE guidelines, at least 35 000 individuals in Birmingham alone may be suitable for surgery. Numbers currently assessed are limited due to lack of resource and expertise. This audit reviewed baseline characteristics of patients referred for specialist obesity and bariatric services...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Obesity occurs as a consequence of increased adipocyte size (hypertrophy) and number (differentiation or hyperplasia). Whilst differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, the molecular mechanisms that underpin the differences in adipose tissue biology and the depot specific metabolic risks that th...

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulphate ester, DHEAS have been shown to oppose the effects of glucocorticoids, thereby producing beneficial effects on insulin sensitivity in rodent models of diabetes and obesity and in hypoadrenal patients. Glucocorticoids, key regulators of adipose differentiation and insulin sensitivity, are reactivated locally by 11β-hydroxysteroid dehydrogenase type (11β-HSD1) oxoreductase activity, which increases with...

Salivary cortisol (SalC) potentially has advantages over serum cortisol (SerC) as it is easier to collect and possibly reflects unbound (free) cortisol. SalC levels are approximately 10 times lower than SerC and require high measurement precision best addressed by liquid chromatography–tandem mass spectrometry (LC-MS/MS), which in contrast to previously used radioimmunoassays eliminates cross-reactivity by other steroids. We describe the use of LC-MS/MS to evaluate the po...