ESPE Abstracts

Background: Steroid 5-α reductase type 2 (SRD5A2) deficiency is an rare inherited disorder resulting from mutations in the SRD5A2 gene, causing 46,XY DSD (Disorder of Sex Development). The mutated SRD5A2 enzyme can no longer convert testosterone to dihydrotestosterone, which is needed for virilisation of external genitalia.Objective and hypotheses: To describe the phenotype, investigations and management of SRD5A2 deficiency.<p class="a...

Background: Transcription activator-like effects nucleases (TALENs) have recently been developed as an efficient method for in vivo genome engineering. Zebrafish are becoming an increasingly popular model to study translational aspects in endocrinology. The redox cofactor ferredoxin (FDX1) is essential for mitochondrial cytochrome P450 (CYP) enzymes including those required for steroidogenesis. In vitro, FDX1 modifications influence the catalytic rate of ster...

Background: Steroid 21-hydroxylase deficiency (21OHD) is the most common form of congenital adrenal hyperplasia. Patients present with cortisol and aldosterone deficiency as well as with hyperandrogenism, leading to virilisation in females and early adrenarche in both sexes. Requiring life-long glucocorticoid (GC) replacement, patients frequently experience daily fluctuations between GC overexposure and deficiency. Increased prevalence of metabolic disease con...

The zebrafish is established as an important model system for studying development and disease, and characterisation of the developmental and functional roles of steroids is crucial for its effective employment in this remit. Whilst oestrogens are known to be essential for female development in zebrafish, the roles of androgens in the development, maintenance and function of the male reproductive system remain unclear.In order to investigate these proces...

Cytochrome P450 side-chain cleavage enzyme, encoded by the CYP11A1 gene, catalyzes the first and rate-limiting step of steroid hormone biosynthesis. Previous morpholino knockdown studies described the divergent functions of the two cyp11a paralogs in zebrafish. Cyp11a1 has been suggested to be required for early development, whereas cyp11a2 is a functional equivalent of human CYP11A1 and is essential for the initiation and maintenan...

Increasing evidence suggests that the aetiology of disorders of sex development cannot be solely explained by genetic alterations. It is highly likely that environmental factors hitting susceptible genetic backgrounds are partly causative. Zebrafish sex is highly plastic during development, 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...

Glucocorticoids regulate a wide range of biological processes including metabolism. Patients with adrenal insufficiency show impaired glucocorticoid biosynthesis either caused by adrenal defects (primary adrenal insufficiency) or by defects in the pituitary gland or hypothalamus (secondary or tertiary adrenal insufficiency). The systemic consequences of differentially disrupted steroid hormone biosynthesis remain unclear. Increasing evidence suggested steroid hormone precursor...

Introduction: The Short Synacthen Test (SST) is the most popular diagnostic investigation of adrenal insufficiency (AI) amongst adult and paediatric endocrinologists. AI can present insidiously and symptoms may be non-specific. The number of medical indications for glucocorticoids is growing and SST usage is correspondingly increasing. There is evidence that an early morning plasma cortisol (EMC) of below ~100–150 nmol/l is highly predictive of failing the SST and the cor...

Introduction: The Short Synacthen Test (SST) is the most popular diagnostic investigation of adrenal insufficiency (AI) worldwide. Symptoms of AI are frequently non-specific, often delaying diagnosis, however fortunately cases of adrenal crisis remain relatively rare. Diagnostic cut-offs for plasma cortisol on SST are controversial, made more complicated by modern assays and paediatric normative values extrapolated from adult data. Some advocate a division between biochemical ...

Introduction: Congenital adrenal hyperplasia (CAH) is the underlying diagnosis in most newborns presenting with 46,XX disorders of sex development (DSD). Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of CAH caused by inactivating mutations in the POR gene. POR is a crucial electron donor to all microsomal type 2 P450 cytochromes (CYPs), including 21-hydroxylase (CYP21A2) and 17alpha-hydroxylase (CYP17A1). The hallmark feature of PORD is combined sex-steroid a...