Endocrine Abstracts

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...

Mitochondrial steroidogenic cytochrome P450 (CYP) enzymes, such as P450 side-chain cleavage, rely on electron transfer from the redox partner ferredoxin (FDX1) for catalytic activity. Previous in vitro data suggest these cofactors are key regulators of CYP enzyme activity. This study aims to establish the role of redox regulation on steroidogenesis using zebrafish as a vertebrate in vivo model.In contrast to humans, zebrafish have two F...

Steroids present in human serum can be used to identify a number of conditions such as congenital adrenal hyperplasia, Addison’s disease and Cushing’s disorder. Historically this has been completed using immunoassays; currently there is a move towards mass spectrometry which reduces analysis time, cross reactivity and improves sensitivity. When mass spectrometers are coupled with liquid chromatography systems (LC–MS) it is possible to monitor a number of steroid...

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...

Background: In women, androgen excess is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Androgen precursors are released from the adrenal gland and converted to active androgens in peripheral tissues including adipose tissue. Although the liver plays a key role in all metabolic processes in the body, its involvement in androgen metabolism is yet to be explored. Here, we describe the investigation of androgen metabolism in human liver using norm...

Background: The urinary steroid metabolome is considered the fingerprint of adrenal gland function. Novel methods using mass spectrometry profiling have seen the advent of a new era for metabolomics with powerful implications for both diagnostics and discovery. Its interpretation is difficult and performed by few specialists with the expertise to do so. This makes it a relatively inaccessible tool for the majority of Clinical Endocrinologists.Objective: ...

Background: Mutations of 21-hydroxylase (CYP21A2) cause congenital adrenal hyperplasia. Its severe (classic) form constitutes a life-threatening disease. Patients suffer a significant disease burden due to co-morbidities that are often treatment-related. The current therapeutic situation is unsatisfying and demands novel treatment approaches. In silico modelling suggests protein misfolding and intracellular retention to play a significant role in the pathogenesis of C...

Context: Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure and occurs predominantly in obese premenopausal women. Signs and symptoms of polycystic ovary syndrome (PCOS) often coexist in IIH. Here we compared the androgenic and metabolic phenotypes in IIH, PCOS and simple obesity.Patients and Methods: We studied 25 patients with IIH (mean age 34.4±9.2 years; mean BMI 37.8±5.2 kg/m2), in comp...