Endocrine Abstracts

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...

Introduction: Aldosterone is a potent adrenal steroid hormone which regulates renal sodium reabsorption and potassium secretion. Clinically, measurement of aldosterone is important to identify patients with primary hyperaldosteronism, and has traditionally been performed by immunoassay. The specificity of immunoassays is often poor due to antibody cross reactivity to other structurally related steroid hormones, resulting in falsely elevated concentrations. To overcome these li...

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...

Introduction: We have developed a highly sensitive LC–MS assay in an attempt to improve the measurement of salivary testosterone in female samples.Methods: A 200 μl saliva sample, calibrators or QC were mixed with 10 μl working internal standard (0.1 μg/l) and 1 ml of methyl tert-butyl ether (MTBE). Vortex mixed for 4 min and frozen at −80 °C (1 h). Unfrozen organic layer was transferred to a glass tube and evaporated. The ...

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...

Anti-inflammatory salicylates improve insulin sensitivity, however the mechanism remains unclear. We have observed down-regulation of the glucocorticoid regenerating enzyme 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) by salicylates in cultured adipocytes and in human adipose tissue after oral salsalate therapy, consistent with known transcriptional regulation of 11βHSD1 by pro-inflammatory cytokines. Since inhibition of 11βHSD1 improves insulin sensitivity...