Endocrine Abstracts

Background: Current evidence suggests that testosterone acts as a vasodilator in several vascular beds. This may have implications for men who are androgen deficient, in whom vascular reactivity may be impaired. We have studied vascular responses in vitro in femoral arteries from testicular feminised mice (Tfm), which lack a functional androgen receptor and are consequently androgen resistant and have reduced circulating levels of testosterone. Methods: Femoral arteries from m...

Testicular feminised (Tfm) mice bear an X-linked, single base pair deletion in the gene encoding the classical androgen receptor(1) consequently these animals express a truncated, non-functional form of the receptor protein. Affected animals (XTfmY) are rendered insensitive to actions mediated via this receptor. The Tfm mouse is therefore an excellent model for studying non-genomic testosterone signalling mechanisms. Unfortunately, Tfm mice are also deficient in the...

Background: Testosterone acts as a coronary vasodilator, and improves myocardial ischaemia in men with coronary artery disease. The dilatory mechanism of testosterone is independent of the classical androgen receptor and also of the release of endothelial-derived vasodilators. The aim of the present study was to determine whether testosterone has any demonstrable calcium antagonistic action, and if so to determine whether this is via inhibition of voltage-operated calcium chan...

Background: Testosterone is a coronary vasodilator, and improves myocardial ischaemia in men with coronary artery disease. The dilatory mechanism of testosterone is independent of the classical androgen receptor and endothelial-derived vasodilators. The aim of this study was to determine whether testosterone increases cAMP production in vascular smooth muscle cells (VSMCs) derived from the primary culture of rat thoracic aortae or in a VSMC cell line (A7r5).<p class="abste...

Background: The testicular feminised (Tfm) mouse exhibits an X-linked single base-pair deletion in the gene encoding the androgen receptor. Gene transcription produces a truncated form of the receptor protein, which has a conformational change in the androgen binding site, preventing androgen binding. Affected male animals (XTfmY) are rendered androgen insensitive and 17-alpha hydroxylase deficient, a key enzyme in the steroidogenesis pathway. XTfmY males have reduced circulat...

The most important cause of death as men age is cardiovascular disease and as men age so their androgen status declines. Studies have shown that lowering of endogenous androgen by deprivation therapy as treatment for prostate cancer increases the risk of cardiovascular death. In long term studies, low blood testosterone is associated with accelerated atherosclerosis as manifest in coronary, aortic and carotid vascular territories.Animal models of hypogon...

Testosterone deficiency is associated with several cardiovascular risk factors. Testosterone replacement therapy (TRT) improves insulin sensitivity, inflammation and cholesterol. Liver X receptor (LXR) is a nuclear receptor which regulates lipid and glucose metabolism, stimulates cholesterol efflux and ApoE, and suppresses inflammation. LXR agonists cause hepatic steatosis but protect against atherosclerosis. TRT attenuates high-cholesterol diet-induced hepatic steatosis in th...

Testosterone deficiency is a common in men with type two diabetes (T2D). We have shown testosterone replacement therapy (TRT) improves insulin resistance and glycaemic control. The mechanisms by which testosterone mediates this action are unknown but may be due to a combination of effects on muscle, liver and adipose tissues. This study investigates the expression of Glut4 and HK2, (two key proteins involved in insulin sensitivity) in muscle tissue of the testicular feminised ...

Background: Low testosterone levels are a common finding in men with type 2 diabetes and are also associated with low HDL cholesterol (HDL-C) levels which are an independent risk factor for cardiovascular disease. The androgen receptor CAG repeat polymorphism (AR CAG) and GGN repeat polymorphism (AR GGN) affect receptor function such that shorter AR CAG and AR GGN=23 are associated with greater transcriptional activity in vitro.Methods and results...

Type 2 diabetes mellitus is associated with increased incidence of low serum testosterone levels in men. Testosterone is known to be positively correlated with insulin sensitivity. Rosiglitazone is an insulin sensitizing agent that reduces insulin resistance by binding to PPAR gamma receptor. The purpose of this study was to determine the effect of Rosiglitazone on testosterone levels in hypogonadal men with Type 2 diabetes.This study was approved by BDG...