Endocrine Abstracts

Congenital adrenal hyperplasia (CAH) is one of the most common inherited disorders. The majority of CAH cases are due to 21-hydroxylase deficiency (21-OHD) caused by mutations in CYP21A2. Because of the profound impact of steroids on physiology and gene expression, the imbalances in steroid hormones resulting from 21-OHD are supposedly leading to a whole-organism response on transcriptome and metabolome level. The systemic consequences of severe 21-OHD during early development...

Steroid hormones are important regulators of many physiological processes. The steroid precursor pregnenolone is converted through several enzymatic steps into all types of steroids, including the stress hormone cortisol. Mitochondrial steroidogenic cytochrome P450 (CYP) enzymes crucially relying on electron transfer from the redox partner ferredoxin (FDX1) are involved in key steps of the cortisol biosynthesis pathway.Cortisol is well-known regulator of...

Although a complex metabolic pathway for vitamin D exists, serum measurement of inactive 25-hydroxyvitamin D3 (25OHD3) continues to be the most common determinant of vitamin D ‘status’. However, several other metabolites contribute to the physiological role of vitamin D, notably the active form 1α,25-dihydroxyvitamin D (1α,25(OH)2D3), inactive 3-epi-25OHD3 and chiral 23R and 24R,25(OH)2D3 metabolites. Quantification of these additional metabolites could pro...

Insulin resistance and androgen excess are the cardinal features of polycystic ovary syndrome (PCOS). The severity of hyperandrogenism and metabolic dysfunction in PCOS are closely correlated, but underlying mechanisms remain poorly understood. Aldoketoreductase type 1C3 (AKR1C3) is an important source of adipose androgen generation, activating androstenedione to testosterone (T). We postulated that AKR1C3 plays a critical role linking androgen metabolism and...

Introduction: Prostate cancer (PC) is dependent on androgen receptor (AR) activation by its canonical ligands testosterone and 5α-dihydrotestosterone (DHT). Intratumoural androgens persisting after castration give rise to castration-resistant PC (CRPC). These intraprostatic androgen levels are hypothesized to result from either adrenal androgen conversion or intratumoural de novo DHT synthesis through the classic or alternative pathways. Quantifying the steroid f...

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...

Advances in trauma care have improved survival resulting in more severely injured individuals surviving to enter the trauma care pathway. A significant threat to recovery is now the dysregulated immune response to injury. The hyperinflammatory response of the innate immune system (SIRS), combined with immunoparesis, leads to complications such as multi-organ failure and sepsis. Moreover, recovery from trauma is significantly affected by age, which may be due to changes in the ...

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...

Background: Glucocorticoids are frequently used to treat childhood inflammatory disorders, and may cause increased fracture predisposition with reduced bone mineral density (BMD), particularly from trabecular bone loss. The contribution of the underlying inflammatory disease processes to these outcomes is poorly understood. Childhood nephrotic syndrome (NS) is a useful model to investigate the effects of steroids on bone, as recurrent courses are often required, but systemic i...

Background: It is well established that subclinical hypothyroidism (SCH) is associated with mild ventricular dysfunction and early cardiovascular disease (CVD), but it is unknown if there is an underlying defect in cardiac bio-energetic function.Objective: To quantify the cardiac phosphocreatine/ATP (PCr/ATP) ratio in SCH, compare with healthy controls (HC) and to measure the effect of 6 months of thyroxine treatment.Method: Cardia...