Endocrine Abstracts

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...

Introduction: It is postulated that uptake rates for gestational diabetes mellitus (GDM) screening would be improved if offered in a setting more accessible to the patient. However, this has not been previously investigated, nor has the feasibility or the acceptability of such an alternative. The aim of this study is to evaluate the rate of uptake of GDM screening in the primary vs secondary care setting, and to qualitatively explore the providers’ experience of primary c...

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...

Diabetes insipidus is a disorder characterised by severe liquid-imbalance because of the inability to concentrate urine. Inactivating mutations in either arginine vasopressin receptor type 2 (AVPR2) or aquaporin 2 (AQP2) gene can cause congenital Nephrogenic diabetes insipidus (NDI). AVPR2 is a G protein-coupled receptor (GPCR) and is mainly expressed at the basolateral site of the kidneys collecting duct principal cells. Activation of this receptor by vasopressin is responsib...

Mutations in CYP11A1, like those in STAR cause lipoid congenital adrenal hyperplasia manifesting with adrenal and gonadal insufficiencies along with derangements of the renin/angiotensin system. Increased adrenal size is usually a feature of STAR but not of CYP11A1 mutation. Milder forms presenting without all of these features have also been described. We present six patients from four families with CYP11A1 mutations discovered by ...

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 ...

Adaptor protein-2 (AP2) is a heterotetramer of α, β, μ, and σ subunits that is pivotal in clathrin-mediated endocytosis and facilitates internalisation of plasma membrane constituents such as the calcium-sensing receptor (CaSR). AP2 σ subunit (AP2σ) missense mutations (Arg15Cys, Arg15His and Arg15Leu) result in familial hypocalciuric hypercalcaemia type 3 (FHH3) and decrease the sensitivity of CaSR-expressing cells to changes in extracellular calc...