Endocrine Abstracts

The enzyme 5β-reductase (AKR1D1) controls intra-cellular steroid hormone availability through hormone clearance. Additionally, it catalyses an essential step in bile acid (BA) synthesis. Disturbances in steroid hormones and BA metabolism have potent effects on metabolic health, therefore we hypothesize that AKR1D1 may play a role in metabolic homeostasis; the role of AKR1D1 in regulating glucose homeostasis and pancreatic function remains unexplored. We generated a global...

Steroid hormones and bile acids are potent regulators of metabolic phenotype. The enzyme 5β-reductase (AKR1D1) has a crucial role in bile acid synthesis and also generates 5β-reduced dihydrosteroid metabolites, regulating intra-cellular steroid availability though the clearance of cortisol, testosterone, androstenedione, and progesterone. As AKR1D1 sits at the interface of bile acid synthesis and steroid metabolism, we have hypothesised that it plays a key role in me...

Introduction: Idiopathic intracranial hypertension (IIH) occurs in young obese women (>90%) but little is known about the metabolic characteristics in these patients. We aimed to characterise IIH fat distribution, metabolic phenotype and evaluate alterations following weight loss.Methods: IIH and matched (BMI/sex) healthy obese controls were recruited. Metabolic indices (fasting lipid, glucose, insulin), anthropological measures and body composition ...

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

Introduction: We present a 5-year-old girl with thyroid hormone resistance, subsequently discovered to be heterozygous for TRβ mutation. This case highlights the necessity to investigate, in detail, all children with persistently high thyroxin with normal TSH levels in order to aid future management and the necessity to follow them up.Case report: SD was born at term by normal delivery weighing 3.34 kg (50th centile). She was referred at 6 months of...

Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis. The A-ring reductases (5α-reductase type 1 (5αR1) and 2 (5αR2)) generate dihydrotestosterone from testosterone, but importantly also inactivate cortisol and are highly expressed in human liver. We propose that 5αR may regulate GC exposure and therefore may modulate metabolic phenotype in human liver.Primary human hepato...

Introduction: There is growing evidence that 11β-HSD1 expression/activity increases with age in key target tissues including adipose tissue, bone, and skin, implicating local amplification of glucocorticoids in the pathophysiology of related disease. We have previously shown that 11β-HSD1KO mice are protected from both the adverse metabolic effects of excess glucocorticoids and age-associated muscle weakness. We investigated changes in global activity and skeletal mu...

2–3% of the UK population are prescribed glucocorticoid (GC) therapy and their adverse effects contribute to a significant health burden. Suppression of endogenous GC secretion is a recognized complication of therapy, but the magnitude of the problem, together with its clinical consequences have not been determined. We conducted a retrospective study across all specialties in a large secondary–tertiary care center identifying 2782 patients who underwent 3666 250 &#95...

The primary function of brown adipose tissue (BAT) is to use lipids to generate heat through uncoupling of oxidative phosphorylation in mitochondria. Glucocorticoids (GC) have a negative effect upon BAT through inhibition of uncoupling protein 1 (UCP1) expression. Similarly, it has been reported that BAT levels decline with age and have been linked to age related accumulation of body fat, leading to the idea that improving BAT function during ageing could have a beneficial rol...

Alstrom syndrome is an autosomal recessive ciliopathy that is characterised by increased body mass index, type 2 diabetes, retinal dystrophy, sensorineural hearing loss, cardiac fibrosis, and chronic kidney disease. Non-alcoholic fatty liver disease (NAFLD) in Alstrom patients ranges from simple steatosis, steatohepatitis and ultimately to fibrosis and cirrhosis. Nafld fibrosis score (http://nalfdscore.com/), enhanced liver fibrosis (ELF)-panel blood tests and Fibroscans are n...