Endocrine Abstracts

Ageing is associated with decline in mitochondrial function whereby dysregulation in carnitine metabolism is highly correlated to poor ageing phenotypes. L-Carnitine transports activated long-chain fatty-acids (FAs) across mitochondrial membranes for β-oxidation and energy production. It is hypothesised that accumulation of long-chain FAs within cells is related to disordered transportation and reflects lower cellular energy upon ageing. Our global aim is to determine the...

Autotaxin (ATX) is a secreted enzyme that generates the lipid signalling molecule LPAs from LPCs. The ATX/lPA axis is strongly linked to fibrotic diseases and therapeutic inhibitors are in development. Assessing the balance of LPC/lPA in diseased target tissues is critical to inform pharmacokinetics/pharmacodynamics (PK-PD) and predict efficacy of ATX inhibitors in vivo. Mass spectrometry imaging (MSI) allows concomitant measurement of multiple molecules with histopat...

Aldosterone and glucocorticoids stimulate sodium transport by the renal tubule, which is important for blood pressure homeostasis. Corticosteroid excess and/or abnormal steroid hormone activity within the kidney can cause hypertension. Circulatory and urinary steroid concentrations can be measured routinely but steroid concentrations at a tissue and cellular level are largely unknown, and the kidney remains a “black box”. Mass spectrometry imaging (MSI) permits local...

Blood pressure homeostasis is regulated via renal sodium reabsorption by aldosterone and glucocorticoids, although the role of glucocorticoids is less clear. High-salt diets lead to suppression of aldosterone in plasma, but changes in available ligands for the mineralocorticoid and glucocorticoid receptors in kidney subregions are unknown. Hypothetically, high-salt intake modifies aldosterone and corticosterone amounts in specific kidney subregions. Kidney cryosections from ma...

Atherosclerotic cardiovascular disease (ASCVD) is a chronic inflammatory disorder characterised by the gradual build-up of plaques in the arterial wall. Unstable plaques are more dangerous than stable plaques as they are prone to rupture and obstruct blood flow, resulting in heart attacks and strokes. Lipids play a key role in plaque progression, yet their exact involvement remains elusive. We hypothesise that stable or unstable plaques will have distinct spatial lipid phenoty...

Pulmonary arterial hypertension (PAH) is a devastating disease characterised by increased pulmonary arterial pressures due to clustered proliferation of cells within the vessel. Untreated this leads to right heart failure and premature death. PAH predominates in females implicating sex hormones, in particular estrogenic metabolites, as being key in the progression of PAH phenotypes. We hypothesised that hydroxy and methoxy estrogens, with known proliferative and anti-prolifera...

Neurosteroids are synthesized locally within the central nervous system and play essential roles in modulating neuronal activity and various brain functions. They can have a wide range of effects, including anxiolytic, sedative, analgesic, and neuroprotective actions. Understanding their distribution in the brain and how they interact with neurotransmitter systems is of significant interest to researchers studying brain function and related disorders. We aim to construct a 3D ...

Excess action of glucocorticoid hormones is implicated in metabolic disease and cognitive decline, 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) catalysing generation of active glucocorticoid hormones in tissues. The penetration rates and tissue-specific contribution of 11βHSD1 to glucocorticoid turnover were assessed using tracer kinetics. 9,11,12,12-d4-Cortisol (d4F) was infused (1.75 mg/day, 7 days) into C57Bl6/J male mice and mice lacking 11βHSD1 (n<...

Atherosclerosis, a multifaceted cardiovascular disease characterised by fatty plaque buildup in large and medium-sized arteries, is a leading cause of heart attacks, strokes and peripheral arterial disease. Its global impact on morbidity and mortality rates poses a significant health challenge. This study aimed to comprehensively understand its complex pathogenesis using histologically aided Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) to e...

Glucocorticoids (GCs) protect cardiomyocytes immediately after myocardial infarction (MI), but GCs subsequently regenerated within the heart by 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) are detrimental during infarct repair, with functional outcomes post-MI improved in mice lacking 11βHSD1. Pharmacological 11βHSD1 inhibition (AZD8329 50mg/kg, 11βHSD1i) was compared to standard clinical therapy (SCT) in a translational pig model (female, 11βHSD1...