Endocrine Abstracts

The phenotypic similarities between patients with Cushing’s syndrome and obesity have highlighted the potential pathogenic role of glucocorticoids in obesity / metabolic syndrome. However circulating cortisol levels in these conditions are normal. At a tissue specific level, the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) controls cortisol availability to the glucocorticoid receptor (GR). In liver and adipose tissue, the type 1 isoform alone is expressed (...

Non-alcoholic fatty liver disease (NAFLD), more recently renamed metabolic dysfunction associated steatotic liver disease (MASLD), is the most highly prevalent chronic liver condition and is associated with significant adverse outcomes, both through liver-specific morbidity and mortality, but perhaps more importantly, through adverse cardiovascular and metabolic outcomes. MASLD is a spectrum of disease, extending from simple steatosis, through to inflammation and fibrosis and ...

Background: The short Synacthen test (SST) is the most widely used dynamic assessment of adrenal reserve. In some situations, the SST may be difficult to perform. Random basal cortisol levels could provide an alternative screening assessment to rationalize which patients need dynamic testing. This is highly clinically relevant, given the large numbers of patients taking prescribed glucocorticoids who are at risk of iatrogenic adrenal suppression.Methods:...

Glucocorticoids (GC), such as prednisolone, are widely prescribed for their anti-inflammatory and immunosuppressive properties. However, they have significant side-effects including insulin resistance and hepatic steatosis. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts 11-dehydrocorticosterone (11DHC) to active corticosterone (CORT) and thus amplifies local GC action. We hypothesise that enhanced local GC regeneration of exogenously administered GCs by ...

5α reductases 1 and 2 (SRD5A1 and SRD5A2) metabolise cortisol into inactive 5α-dihydrocortisol contributing to the regulation of cortisol availability in addition to their established role in the generation of dihydrotestosterone from testosterone. Dutasteride and finasteride are commonly prescribed to patients with benign prostatic hyperplasia but their potential metabolic effects have only recently been identified. Dutasteride inhibits both SRD5A1and SRD5A2 whilst ...

Non-alcoholic fatty liver disease (NAFLD) is the most highly prevalent chronic liver condition and is associated with significant adverse outcomes, both through liver-specific morbidity and mortality, but perhaps more importantly, through adverse cardiovascular and metabolic outcomes. NAFLD is a spectrum of disease, extending from simple steatosis, through to inflammation and fibrosis and risk of cirrhosis. The mechanisms that govern hepatic lipid accumulation and the predispo...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. It represents a spectrum of disease, ranging from steatosis to non-alcoholic steatohepatitis, progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. BAs, as well as their intermediary products (oxysterols), are metabolic modulators exerting their effects through activation of nuclear receptors (NRs), including the farnesoid-X- (FXR) and liver-X-receptors (LXR). Cruciall...

The hepatic enzyme 5β-reductase (AKR1D1) sits at the interface between two metabolic pathways, converting steroid hormones to their inactive 5β-reduced metabolites during steroid clearance, and as a step in the synthesis of bile acids from cholesterol. Both the steroid substrates and the bile acid products of AKR1D1 are potent hormones that regulate hepatic energy metabolism and inflammation. It is not known how these two functions are spatially organised within hepa...

Hepatocellular carcinoma (HCC) is the 6th most common form of cancer and the 4th most common cause of cancer related death. AKR1C1 is a member of the aldo-keto reductase 1C (AKR1C) subfamily and has important roles in steroid hormone metabolism and in reducing lipid peroxides. AKR1C1 is ubiquitously expressed, with high levels of expression in the liver. Studies have identified differential expression in HCC with high levels of AKR1C1 expression associate...

Dysbiosis of the gut microbiome contributes to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Reduced diversity and composition of the microbiome are associated with increased intestinal barrier permeability, increased bacterial translocation and NAFLD progression. The ALIOS diet in rodents replicates many of the metabolic and histological features of NAFLD in humans and here we report the effect of the ALIOS diet on the gut microbiome. Male and female C57BL/6 ...