Endocrine Abstracts

Insulin resistance and androgen excess are the cardinal features of polycystic ovary syndrome (PCOS). Severity of hyperandrogenism and metabolic dysfunction in PCOS are closely correlated, but underlying mechanisms remain poorly understood. Aldoketoreductase type 1C3 (AKR1C3) is a key source of adipose androgen generation, activating androstenedione to testosterone (T). We postulated that AKR1C3 plays a critical role linking androgen metabolism and metabolic ...

Context: Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure and occurs predominantly in obese premenopausal women. Signs and symptoms of polycystic ovary syndrome (PCOS) often coexist in IIH. Here we compared the androgenic and metabolic phenotypes in IIH, PCOS and simple obesity.Patients and methods: We studied 25 patients with IIH (mean age 34.4±9.2 years; mean BMI 37.8±5.2 kg/m2), in comp...

Context: Androgen excess, obesity and hyperinsulinaemia are the cardinal features of polycystic ovarian syndrome (PCOS). While several studies have addressed the relationship between androgen excess and hyperinsulinaemia, the link between androgen excess and fat distribution remains largely undefined. Recent work has highlighted the importance of adipose tissue as an organ of androgen activation. Here, we evaluated the relationship between visceral fat and androgen excess in w...

Background: Excess glucocorticoid (GC) exposure is associated with an adverse body composition and metabolic profile characterised by increasing fat mass, muscle atrophy, insulin resistance, fatty liver, and dyslipidaemia culminating in increased cardiovascular risk. GCs are widely prescribed with increasing age where their effects can have deleterious effects.Objectives: To investigate the impact of GC exposure on subcutaneous adipose lipid metabolism a...

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, insulin resistance, and androgen excess. Hyperandrogenism may correlate with metabolic risk but PCOS consensus criteria currently define androgen excess on the basis of serum testosterone only. Here we studied the utility of the androgen precursor serum androstenedione in conjunction with serum testosterone as a predictor of metabolic dysfunction in PCOS.86 PCOS patients fulfilling Rott...

There are 1.21 million deaths from road traffic accidents worldwide. In Afghanistan, there have been 2005 battle injuries over 10 years. Advances in military trauma care have improved survival, resulting in more severely injured individuals entering the trauma care pathway. Improved understanding of endocrine-immune changes after severe trauma may facilitate novel interventions to improve outcomes. We prospectively recruited 102 severely injured patients at the Queen Elizabeth...

In the pathogenesis of obesity, dysregulated tissue cortisol metabolism (controlled by 11β-HSD1), is postulated to be involved. Fifteen patients (seven mens, mean BMI 50.8±7 kg/m2) awaiting Roux En Y gastric Bypass (RYGB) surgery underwent assessment of 11β-HSD1 activity using cortisol generation profile. Corticosteroids in serum and subcutaneous adipose tissue microdialysis fluid and urinary corticosteroid metabolites were analysed by liquid and gas ...

Zebrafish has emerged as an important vertebrate in vivo model to study human disease. Steroidogenesis in zebrafish is not well characterised. Human CYP11A1 (hCYP11A1) catalyses the first step of steroidogenesis, the conversion of cholesterol to pregnenolone. Zebrafish Cyp11a1 (zCyp11a1) is essential during embryogenesis. Published data suggest that zCyp11a1 facilitates steroidogenesis in the interrenal (equivalent to mammalian adrenal), gonad and brain. We identified...

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individuals, with nor...

Mitotane (o,p’DDD) is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumour. Mitotane is considered an adrenolytic substance, but no information is available regarding distinct steroidogenic effects. Here we carried out steroid metabolomics by gas chromatography/mass spectrometry in 24-hour urine samples from 106 patients with ACC and with samples coll...