Endocrine Abstracts

Glucuronidation is an enzymatic process that terminally inactivates steroid hormones, including estrogens and androgens, thereby influencing carcinogenesis in hormone-dependent cancers. While estrogens drive breast carcinogenesis via the estrogen receptor alpha (ERα), androgens play a critical role as prohormones for estrogen biosynthesis and ligands for the androgen receptor (AR). Herein, the expression and regulation of two androgen inactivating UDP-glucuronosyltransfer...

The balance of androgen and estrogen hormone activity determines the degree of breast development in males and females. A predominance of androgen action impedes whereas a predominance of estrogen action promotes breast development. This sex hormone antagonism is mechanistically mediated by androgen and estrogen receptors (AR, ER). The alpha form of ER (ERα) is required for normal breast development and is the driving oncogene in the majority of breast cancers. The AR is ...

All characteristic metabolic properties of a bio-fluid, cell, tissue or an organism are described by its metabolome, which is the functional readout of the genome and proteome. Metabolomics is the newest member in the “omics” cascade investigating the metabolome within a specific biological matrix (e.g. serum, tissue, cells or CSF) offering the possibility of assessing the relationship of a genetic modification to a specific desired phenotype in an effort to determin...

Objective: The purpose of this study was to evaluate the psychometric properties of a novel, patient-reported outcome (PRO) measure, the Hypoparathyroidism (HPT) Symptom Diary (HPT-SD), using data collected during a cross-sectional, noninterventional, observational study. The HPT-SD, developed according to the US Food and Drug Administration PRO guidance, addresses the severity of key symptoms (muscle cramping, tingling and muscle spasms/twitching, fatigue, cognition, emotions...

Glucocorticoid (GC) production rates are elevated in obese, insulin resistant individuals. We and others have demonstrated decreased hepatic cortisol regeneration through reduced 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity that converts inactive cortisone to cortisol. In addition, there is enhanced cortisol clearance by A-ring reductases, (notably 5α-reductase). We have argued that these changes drive the hypothalamo-pituitary–adrenal axis a...

Early life events can have short and long-term effects on neuroendocrine, autonomic, and behavioural responses to stress and appear to play an important role in the etiology of stress-related disorders. Glucocorticoids are thought to be key mediators of these brain-endocrine-immune connections. We investigated the effects of a short-term social isolation (4 h) of domestic piglets at different days of age (7, 21, 35) both on behavioural alterations in open-field tests and on mo...

The use of more tissue-mimetic 3-dimensional (3D) cell culture models for in vitro drug screening has significantly increased in the past with the expectation to overcome with over-interpretation of drug effects obtained with conventional 2D cultures. In this study, we characterized 3D prostate cancer (PCa) organoids where PCa epithelial cells (LNCaP, DuCaP, LAPC4) were cultured alone or with PCa-associated fibroblasts (CAFs) in 96 well hanging drop plates in order to...

Increased adiposity is associated with insulin resistance, type 2 diabetes and metabolic dysfunction. Altered adipokine secretion, changes in local and systemic glucocorticoid metabolism and increased inflammation have all been postulated as contributory mechanisms. We have previously described changes in subcutaneous adipose tissue (SAT) gene expression that are associated with obesity and glucose intolerance in cross-sectional studies. However, the effects of longitudinal ch...

Background: Excess glucocorticoid (GC) exposure is associated with an adverse body composition and metabolic profile characterised by increasing fat mass, muscle atrophy, insulin resistance, fatty liver, and dyslipidaemia culminating in increased cardiovascular risk. GCs are widely prescribed with increasing age where their effects can have deleterious effects.Objectives: To investigate the impact of GC exposure on subcutaneous adipose lipid metabolism a...

Dysregulation of the enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistant states, however longitudinal changes in glucocorticoid metabolism over time have not been investigated. This study was designed to evaluate the role of pre-receptor glucocorticoid metabolism in the development of insulin resistance and obesity. 24 h urinary glucocorticoid and mineralocorticoid metabolites were measured by gas chroma...