Endocrine Abstracts

With the emergence of core facilities across the academic community has come the need for their good management. Increasingly the role of facilities manager has become a promising career route for graduate and post-doctoral scientists.A core facility typically offers state of the art instrumentation, fully serviced and maintained with a high level of expertise in their operation and scientific applications. In terms of a mass spectrometry core facility, ...

Large animals are increasingly used a models for endocrine research. Unlike rodents they are cortisol-dominant and thus more similar to humans. In this study we use two novel analytical methods to compare the steroid profile of pigs, sheep and humans; 1. Simultaneous quantification of primary glucocorticoids, glucocorticoid precursors and mineralocorticoids in plasma (>20 steroids); 2.Quantification of glucocorticoids metabolites (>10 ...

Canrenone and mifepristone (RU486) are respectively mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) antagonists commonly used to block or displace steroid for clinical pharmacological or research purposes. The aim of this study was to develop and validate a sensitive, quantitative assay for the combined analysis of glucocorticoids (cortisol, cortisone, corticosterone, and 11-dehydrocorticosterone), mineralocorticoids (aldosterone), canrenoate, and mifepristone...

Canrenone is a mineralocorticoid receptor antagonist used as a diuretic agent to treat hypertension. It is the major active metabolite of spironolactone and may be quantified in clinical studies either to ensure compliance or to gain information about pharmacokinetic-pharmacodynamic interactions.The aim of this study was to develop and validate a sensitive, quantitative assay for the analysis of canrenone in plasma.HPLC mass spectr...

Background: 5α-Reductase (5αR) catalyses conversion of testosterone to its more potent metabolite dihydrotestosterone (DHT) and is inhibited when treating benign prostatic hyperplasia. 5αR has two isozymes; dual isozyme inhibition with dutasteride gives greater DHT suppression than finasteride, which inhibits only 5αR type 2.Aim: To develop a novel assay to simultaneously analyse testosterone, epitestosterone, DHT, androstenedione, du...

Serum was collected with ethical approval from Vanderbilt Medical Center, USA for blinded analysis between clinical phenotypes; heritable and idiopathic PAH patients (hPAH n=13, 14; iPAH n=7, 12) compared to non-PAH control (n =17, 17) (female, males, respectively). Quantification of circulating estrogens in human bio-fluids may reveal insights into disease aetiology but has been hampered through inadequate sensitivity and specificity of immunoassays...

Background: Adipose tissue dysfunction could partially explain the well-demonstrated association between obesity and survival in breast cancer (BC). Oestrogen and glucocorticoid concentrations and their respective activation enzymes, oestrogenic 17β-hydroxysteroid dehydrogenases (17βHSDs) and aromatase, and 11βHSD1 are increased in adipocyte hyperplasia and hypertrophy, supporting the hypothesis of a potential role for locally generated steroids in obesity-assoc...

Intracellular cortisol is regulated by 11βHSD1. Although the field has focused on regeneration of cortisol from inert cortisone by 11β-reductase activity of 11βHSD1, we have used stable isotope tracers and arteriovenous sampling to quantify simultaneous dehydrogenase (cortisone generation) and reductase (cortisol regeneration) in human adipose and skeletal muscle. In vitro studies suggest insulin regulates this balance of reductase vs dehydrogenase acti...

Synthetic glucocorticoids are administered to pregnant women at risk of pre-term delivery to mature organs and improve neonatal survival. We have shown that glucocorticoid action is essential to mature the fetal heart. Here, we tested the hypotheses that antenatal glucocorticoid exposure, prior to the normal increase in glucocorticoid levels, will advance fetal heart maturation and this will depend on cardiovascular glucocorticoid receptor (GR).Male SMGR...

Congenital adrenal hyperplasia (CAH) is associated with poor health outcomes. This is, in part, because doses of glucocorticoid sufficient to suppress excess adrenal androgens are also associated with adverse metabolic effects such as insulin resistance. This toxicity occurs with efficacious doses of all commonly prescribed glucocorticoids (hydrocortisone, prednisolone and dexamethasone). However, the glucocorticoid corticosterone may have an improved therapeutic index because...