Endocrine Abstracts

Many organs are functionally sexually dimorphic, resulting in profound differences in the activity of several physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The rodent HPA axis matures post-weaning, characterized by parallel increments in adrenal weight, adrenal cortical size and corticosterone secretion. Between postnatal days (PND) 30 to 45, these parameters increase to a greater extent in females compared to males. Over this same interval, h...

Background: Corticosteroid Binding Globulin (CBG) binds >85% of plasma cortisol and controls the circulating free cortisol pool. Proteolytic cleavage by neutrophil elastase is proposed to reduce CBG binding affinity and increase free cortisol availability to inflamed tissues. The CORtisol NETwork (CORNET) consortium found that genetic variation at a locus spanning SERPINA1 (encoding alpha-1 antitrypsin, A1AT, the endogenous inhibitor of neutrophil elastase) and SE...

A genome wide meta-analysis by the CORtisol NETwork (CORNET) consortium1 has identified genetic variants spanning the SERPINA6/SERPINA1 locus on chromosome 14 associated with changes in morning plasma cortisol and predictive of cardiovascular disease (Crawford et al, Unpublished). SERPINA6 encodes Corticosteroid Binding Globin (CBG) which binds most cortisol in blood and influences delivery of cortisol to target tissues. We hypothesised th...

The glucocorticoid (GC) activating enzyme 11β-HSD1 is potently upregulated within macrophages and synovial fibroblasts of inflamed joints, where it increases therapeutic GC signalling and regulates their anti-inflammatory profiles. Whilst in vitro studies have demonstrated the importance of autocrine signalling in this context, the importance of paracrine signalling remains poorly defined. In this study, we examined the role of 11β-HSD1 in paracrine GC signalling bet...

Background: Primary Aldosteronism (PA) is the commonest curable cause of hypertension. Whole exome sequencing (WES) of an aldosterone producing adenoma from a 46-year-old man with resistant hypertension revealed a novel somatic mutation (Val380Asp) of the single transmembrane domain of Cell Adhesion Molecule-1 (CADM1). A Gly379Asp mutation was identified by WES of a PA patient in Munich. Both patients were cured of hypertension by adrenalectomy.Method: A...

Background: Aldosterone producing cell clusters (APCCs) are microscopic pockets of cells in the adrenal zona glomerulosa (ZG), which stain densely for aldosterone synthase (CYP11B2). They exist in 30% of normal adrenal glands and have similar somatic genetic mutations as some aldosterone producing adenomas (APA), especially of CACNA1D. Some APCCs are precursors to APAs. Adrenalectomy for primary aldosteronism (PA) cures hypertension in < 50% of patients, maybe bec...