Endocrine Abstracts

Oestrogens impact colorectal cancer (CRC) development and proliferation. Biologically active oestrogens, oestrone (E1) and oestradiol (E2), are metabolised through hydrolysis of their sulfated forms (oestrone sulfate (E1S) and oestradiol sulfate) by steroid sulfatase (STS). We have shown that increased STS activity drives CRC proliferation via oestrogen hydrolysis. We have also identified that CRC expresses the necessary organic anion transport...

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 ...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, ranging from simple steatosis to the necro-inflammatory disease, non-alcoholic steatohepatitis (NASH). Development of NASH subsequently increases risk of hepatocellular carcinomas (HCC). Alongside the impact on the liver, NASH is associated with other clinical features, including insulin resistance, hyperlipidaemia and sarcopaenia. We demonstrate that mice fed the American lifestyle i...

Circulating oestrogen concentrations affect the incidence of and outcomes for patients with colorectal cancer (CRC). We have previously shown that steroid sulphatase (STS), the fundamental enzyme that liberates conjugated oestrogens into their active forms, is significantly elevated in human CRC tissue. Here we demonstrate that elevated STS activity correlates to increased CRC proliferation, and that these effects are mediated through G-protein coupled oestrogen receptor (GPER...

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). 5β-reductase (AKR1D1) is a liver enzyme that catalyses a fundamental step in bile acid (BA) synthesis. Both BAs and BA intermediates are established as potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial role in NAFLD and HCC. Human liver b...

Oestrogenic effects on colorectal cancer (CRC) incidence, proliferation, and patient survival remains controversial. We have previously shown enzymic pathways favouring oestradiol (E2) synthesis are upregulated in CRC, and stimulation of the G-protein coupled oestrogen receptor (GPER) by E2 increases CRC proliferation. Here we interrogated The Cancer Genome Atlas (TCGA) Colon Adenocarcinoma (COAD) database to determine all oestrogen metabolism enzymes and...

Oestrogenic effects on colorectal cancer (CRC) incidence, proliferation, and patient survival remains controversial. We have previously shown enzymic pathways favouring oestradiol (E2) synthesis are upregulated in CRC, and stimulation of the G-protein coupled oestrogen receptor (GPER) by E2 increases CRC proliferation. Here we interrogated The Cancer Genome Atlas (TCGA) Colon Adenocarcinoma (COAD) database to determine all oestrogen metabolism enzymes and...

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver 5β-reductase (AKR1D1) catalyses a fundamental step in bile acid (BA) synthesis. BAs and BA intermediates are potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial role in NAFLD and HCC. Liver biopsies and serum samples were obtained from healt...

Disruption of the gut-liver axis contributes to metabolic syndrome and the progression of non-alcoholic fatty liver disease (NAFLD). Bile acids (BAs) are potent antimicrobials that support gastrointestinal health and dysregulation of BA homeostasis in NAFLD is thought to contribute to gut dysbiosis. Furthermore, an increase in hydrophobic (cytotoxic) BA species may directly affect gut health. We have previously shown that bile acid synthesis enzyme, 5β-reductase (AKR1D1),...