Endocrine Abstracts

Colorectal cancer (CRC) is the third most common cancer worldwide with incidence expected to rise. Although not traditionally viewed as a hormonal cancer, evidence suggests peripheral synthesis of active oestrogens worsens prognosis. Oestrogen metabolising enzymes include steroid sulphatase (STS), which desulphates oestrogens into their active forms, and 17β-hydroxysteroid dehydrogenases (17βHSD), which are estrogen oxidoreductase enzymes. We have previously shown ST...

Oestradiol (E2) and oestrone (E1) are implicated in many diseases and drive cell proliferation in breast, ovarian, and endometrial cancer. Inactive sulphated oestrogens (E2S and E1S) represent a circulating reservoir forming active de-sulphated oestrogens. Therefore, new methods that accurately measure both sulphated and non-sulphated oestrogen concentrations have potential value for understanding oestrogen-related cancer. We present...

Gas chromatography mass spectrometry (GC-MS) is the gold standard for urinary steroid profiling. Our established GC-MS method quantifies mineralocorticoids, glucocorticoids, and androgens. GC-MS assays require chemical derivatisation and long run times, rendering them unsuitable for high-throughput analysis. Our aim was to develop and validate a high-throughput urinary steroid profiling method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-LC...

Comprehensive multi-steroid profiling offers a powerful tool for the investigation, diagnosis and management of steroidogenic disorders by simultaneously quantifying multiple steroids from several pathways of steroid biosynthesis and metabolism. Difficulties can arise when optimising chromatography and mass spectrometry conditions for many analytes in a single method. Low concentrations of ammonium fluoride have previously been shown to enhance the sensitivity of select analyt...

Background: Development of multi-steroid profiling allows comprehensive investigation into the different branches of steroid metabolism. Immunoassays only allow analysis of a single steroid per assay and suffer from problems with specificity due to cross reactivity of similar steroids. Liquid-chromatography mass spectrometry has the specificity to analyse multiple steroids in a single experiment and the dynamic range to quantify steroids at high concentrations such as those ob...

Pituitary tumor transforming gene (PTTG) binding factor (PBF) is a proto-oncogene which is frequently upregulated in endocrine cancers. PBF has previously been determined to contain several putative signal sequences within its 180 amino acids. Previous studies have shown the nuclear localisation signal (NLS) to be functional and prediction software now suggests the presence of a putative leucine-rich nuclear export signal (NES) between residues 17 and 27. PBF is known to shutt...

Background: Advancements in medical care have significantly improved survival after major traumatic injury and the main risks are now sepsis and multi-organ failure. An understanding of the hormonal, inflammatory and metabolic changes that occur following trauma is still evolving but it is clear that they impact significantly upon patient prognosis. To date, studies that have examined trauma-induced changes in steroid metabolism have analysed samples taken from patients post-h...

Background and aims: HNF1A-MODY causes monogenic diabetes with a lean, insulin sensitive phenotype. Altered glucocorticoid (GC) metabolism has been implicated in the pathogenesis of type 2 diabetes (T2D) and inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which regenerates active cortisol from inactive cortisone have been trialled as a therapeutic approach. 11β-HSD1 is down-regulated in hepatocytes from Hnf1a knock-out mice but the role...

Idiopathic intracranial hypertension (IIH) is a condition of unknown aetiology characterised by raised intracranial pressure, chronic headaches and blindness. Akin to polycystic ovary syndrome (PCOS), IIH patients are almost exclusively obese females of reproductive age. A distinct androgen excess profile has been noted in PCOS. Here, we aimed to delineate androgen metabolism in IIH compared to PCOS and simple obesity.Women w...

Background and aims: HNF1A-MODY causes monogenic diabetes with a lean, insulin sensitive phenotype. Altered glucocorticoid (GC) metabolism has been implicated in the pathogenesis of type 2 diabetes (T2D) and inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which regenerates active cortisol from inactive cortisone have been trialled as a therapeutic approach. 11β-HSD1 is down-regulated in hepatocytes from Hnf1a knock-out mice but the role...