Endocrine Abstracts

Background: Cushing’s syndrome (CS) is caused by endogenous cortisol excess and is associated with significant morbidity. Twenty-four-hour urinary cortisol is one of the most useful tools to diagnose CS although it has limitations, especially in “mild” and “subclinical” forms of cortisol excess. We hypothesized that given the diurnal rhythm of physiological cortisol secretion, night-time urinary glucocorticoid excretion should be lower than day-time ex...

In patients with autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion; patients on long-term steroid replacement have increased morbidity, reduced life expectancy and poorer quality of life. Recent early-phase studieshave demonstrated that some endogenous steroidogenic function – Residual Adrenal Function (RAF) - is maintained at the point of diagnosis in a proportion of AAD patients; this...

Objective: Therapeutic glucocorticoids (GCs) are commonly used in the treatment of chronic inflammatory disease. Unfortunately, their long-term administration is associated with deleterious systemic side effects including muscle atrophy. 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) activates glucocorticoids within muscle, is increased with inflammation, and has previously been shown to mediate GC induced muscle wasting. We examined the role of 11 beta-hydroxyster...

Glucocorticoid (GC) signalling via the glucocorticoid receptor (GR) is essential for normal lung development. Previous work using conditional mouse knockouts of the GR gene established that GR activity in the mesenchymal compartment of the lung is critical for normal respiratory development. Screens for GC-target genes with conditional mesenchymal GR deficient mouse lung (GRmeskO) identified Versican (Vcan), an important extracellular matrix (ECM) component and cell proliferat...

The uterus is an androgen-responsive tissue and AR is expressed in cells within the endometrium and myometrium. We have demonstrated that treatment of ovariectomised mice with the potent androgen dihydrosterone (DHT) induces a uterotrophic response with changes in expression of genes involved in cell-cycle progression, Wnt signalling and an expansion of the glandular epithelium. Selective androgen receptors modulators (SARMs) are AR ligands in development as potential therapeu...

Both therapeutic glucocorticoids (GCs) and chronic inflammation are powerful inducers of systemic bone loss, resulting in osteoporosis and increased morbidity. Whilst GCs suppress inflammation, it is unclear how these factors interact to determine net bone metabolism. We investigated the balance between osteo-protective and osteo-destructive properties of GCs in the TNF-tg model of chronic inflammatory disease. Wild-type (WT) and TNF-tg mice were treated with corticosterone (1...