Endocrine Abstracts

Introduction: AKR1D1 is a 5β-reductase that sits at the interface of steroid hormone metabolism and primary bile acid biosynthesis. 5β-reduced androgens are widely believed to be inactive, but to our knowledge there are currently no data that have directly tested their ability to activate the androgen receptor (AR). We therefore wanted to test the ability of AKR1D1 to regulate androgen availability in vitro and to determine if 5β-reduced androgens are a...

Context: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of classic androgen synthesis. Recent work has highlighted that impaired DHEA sulfation results in enhanced androgen production. Here, we evaluated the relationship between DHEA and DHEAS and androgen excess and metabolic phenotype in PCOS.Patients and methods: We compared 65 women with PCOS to 35 healthy women matched for age and body mass index (BMI). All subject...

Sex development in zebrafish is highly plastic, making this species an ideal model for investigation of endocrine disruption and gonadal development and function. However, the hormonal regulation of these processes in zebrafish is poorly understood. We have used a model of androgen and glucocorticoid deficiency to explore these processes. In humans, ferredoxin (FDX1) is an electron-providing cofactor required for steroid biosynthesis. The zebrafish homologue of FDX1, ...

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...

Polycystic ovary syndrome (PCOS) affects 10% of women and is associated with an increased risk of type 2 diabetes and fatty liver disease. Androgen excess is an important driver of metabolic risk in PCOS. In adipose tissue from women with PCOS, increased activation of androstenedione (A4) to testosterone (T) by the enzyme AKR1C3 results in systemic lipotoxicity. Recent in-vitro studies also demonstrated that T and 11-ketotestosterone (11KT) activate the androgen recep...