Endocrine Abstracts

The enzyme 5β-reductase (AKR1D1) catalyses an essential step in bile acid synthesis. In addition, it controls intra-cellular steroid hormone availability through hormone clearance. As disturbances in steroid hormones and bile acid metabolism have potent effects on metabolic health, we hypothesize that AKR1D1 may play a role hepatic lipid accumulation. We generated global AKR1D1 knockout mice (KO) alongside wild-type controls (WT). Mice were fed either normal chow (NC) or ...

The enzyme 5β-reductase (AKR1D1) catalyses an essential step in bile acid synthesis, but in addition, controls intra-cellular steroid hormone availability by generating 5β-reduced dihydrosteroid metabolites. As disturbances in steroid hormone and bile acid metabolism have potent effects on metabolic health and lipid homeostasis, we hypothesize that AKR1D1 may play a role hepatic lipid accumulation and contribute to the development of metabolic disease. We generated a...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic disease. 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. Steroid hormones, including glucocorticoids, as well as bile acids are established regulators of metabolic phenotype. We hypothesized that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis. Genetic manipulatio...

Introduction: Glucocorticoids (GC) are prescribed to 2–3% of the population of the UK and USA. Their use is associated with a significant side effect profile that includes the development of central obesity, insulin resistance and type 2 diabetes. 5α-reductase (5αR) inhibitors (Finasteride and Dutasteride) are also commonly prescribed in the context of prostate disease, where they inhibit the conversion of testosterone to dihydrotestosterone. Additionally, they ...

Introduction: Abnormal liver function tests (↑LFTs) are frequently observed in Turner’s syndrome (TS), although the aetiology is unclear. Obesity is reported as one of the causes; recently an increased prevalence of elevated GGT was found in TS patients with a ring X karyotype.Aim: To analyse the association between abnormal LFTs and TS-related conditions, and in particular their relationship with the different TS-karyotypes.<p class="abst...

Non-alcoholic fatty liver disease is the hepatic manifestation of metabolic disease. 5β-reductase (AKR1D1) is highly expressed in human and rodent liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. Steroid hormones, including glucocorticoids, as well as bile acids are established regulators of metabolic phenotype. We have hypothesized that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis.<p class...

Introduction: Liver involvement is frequent in Turner’s syndrome (TS). We have shown that 35% TS women have elevated liver function tests (↑LFTs). Most common hepatic changes include steatosis and steatohepatitis; however, progression to advanced fibrosis and cirrhosis is reported. This study assessed a simple noninvasive test for liver fibrosis, FIB-4, which combines standard biochemical values (platelets, ALT, AST) and age in order to evaluate its diagnostic perfo...

Glucocorticoids (GC) are critical to stress adaptation but in excess (Cushing’s syndrome) drive metabolic dysfunction. 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1) amplifies intracellular GC signaling with 11β-HSD1KO mice protected from the side-effects of GC excess. Brown adipose tissue (BAT) function is impaired by GC’s, which repress UCP1 and beta-adrenergic stimulated thermogenesis. Identifying mechanisms regulating BAT function is important a...

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 met...

Introduction: Elevated liver function tests (↑LFTs) are frequent in Turner’s syndrome (TS), with a prevalence between 20 and 80%, and increases with age. Their pathogenesis and clinical significance is unclear.Objectives: To study the prevalence of ↑LFTs and their relationship with karyotype, anthropometric, metabolic and TS-related conditions: 68 TS women, average age 39 years (range 18–61 years), were reviewed.<p class="abstex...