Endocrine Abstracts

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...

Activation of the hypothalamic–pituitary–adrenal (HPA) axis and altered tissue glucocorticoid action in obesity and metabolic syndrome has been attributed to altered peripheral cortisol metabolism. In human obesity, cortisol clearance is increased with up-regulation of A-ring reductases and down-regulation of cortisol-regenerating 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in liver, while in adipose tissue 11β-HSD1 is up-regulated. Rodent studi...

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...

Background: Male hypogonadotrophic hypogonadism is an increasingly common cause of referral to endocrine clinics. Subnormal testosterone levels are frequently observed in obesity, type 2 diabetes mellitus and in the elderly. Endocrine Society guidelines suggest stratification of investigations based on the degree of androgen deficiency, with full pituitary function testing and MRI recommended only in those with serum testosterone levels less than 5.2 nmol/L. However the eviden...

Glucocorticoid excess is associated with increased anxiety and accelerated cognitive decline. Concentrations of glucocorticoids within tissues, including the brain, are influenced by local metabolism. 5α-Reductase 1 (5αR1), expressed in brain, converts corticosterone to its A-ring reduced metabolites, which have a different spectrum of activities. Here, we investigated if mice homozygous for disrupted 5αR1 alleles (5αR1-KO) experience heightened anxiety and...

We recently showed that 5α-reduced metabolites of corticosterone (B), namely 5α-dihydrocorticosterone (5αDHB) and 5α-tetrahydrocorticosterone (5αTHB), possess similar anti-inflammatory properties to B, but have lesser metabolic effects. Here, we explored the anti-inflammatory mechanisms of these 5α-reduced metabolites in vitro. Data are mean % suppression/induction, compared by one way ANOVA, *P<0.05 versus vehicle.<p class="...

Obesity is associated with metabolic and vascular dysfunction. Many models have shown insulin resistance reduces endothelium-dependent vasodilation but this is also seen in obese subjects with normal glucose tolerance. There is also evidence of increased response to vascular injury in obese animals, although the mechanisms underpinning this are not fully understood. This study used a mouse model of diet-induced obesity (DIO) to address the hypothesis that obesity causes metabo...

Background: Visceral fat is a key factor underlying type 2 diabetes. The amount and distribution of body fat is strongly influenced by sex steroids. Androgen receptors (ARs) are present in adipose tissue and are abundant in the detrimental visceral bed. Here, we sought to determine the contribution of the AR in adipose tissue to the pathophysiology of visceral obesity and type 2 diabetes.Methods: Male fat-specific AR-knockout (fARKO) mice (12 weeks; n...

Although obesity affects men and women, the risks of associated metabolic disturbances (e.g. type 2 diabetes) differ between the sexes. Altered peripheral glucocorticoid metabolism may underpin the metabolic consequences of obesity; however, most research exploring this has focused on male animals. This study used a mouse model to investigate the hypothesis that alterations in glucocorticoid metabolism caused by diet-induced obesity (DIO) will be more profound in males than in...