Endocrine Abstracts

Cortisol is regenerated from cortisone by 11βHSD1 reductase in cells from VAT. Mice overexpressing 11βHSD1 in adipocytes have more glucocorticoids in the portal vein (PV) and hepatic insulin resistance. In humans, hepatic vein (HV) sampling during D4-cortisol tracer infusion confirmed substantial splanchnic cortisol generation, and indirect modelling suggested major contributions from both liver and VAT. PV sampling in dogs, however, did not reveal cortisol release f...

Objective: Aromatase deficiency in mice or men prevents conversion of androgens to oestrogens and results in central obesity and insulin resistance. In idiopathic obesity, higher aromatase mRNA levels in adipose tissue predict peripheral rather than central fat distribution, but any contribution of aromatase to metabolic complications is unknown. Here, we measured plasma steroids in a large cohort of men and post-menopausal women, in whom aromatase is the major source of oestr...

The rate limiting steps of hepatic glucocorticoid clearance are via A-ring reduction by 5α- and 5β-reductases. Our recent in vitro studies suggested that products of 5α-reduction (eg 5α-tetrahydrocorticosterone) can activate glucocorticoid receptors and hence may contribute to glucocorticoid action in liver. Here we compared the effects of administering 5α-tetrahydrocorticosterone (5αTHB) in vivo with those of corticosterone (B)....

PPARgamma-agonists improve insulin sensitivity and discourage visceral fat accumulation but mechanisms remain uncertain. In rodents, PPARgamma-agonists downregulate 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) in adipose tissue (AT), thereby potentially decreasing intra-adipose glucocorticoid (GC) concentrations. We tested whether PPARgamma-agonists regulate 11b-HSD1 in humans, and if their insulin-sensitising effect is GC-dependent.12 healthy m...

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...

Background: Glucocorticoids (GCs) modulate glucose homeostasis by acting on metabolic tissues including liver, adipose and skeletal muscle. GC access to corticosteroid receptors in these tissues is regulated e.g. by pre-receptor metabolism. We recently identified a role for ABCC1, a transmembrane ‘drug-resistance’ transporter, as a GC exporter which limits intracellular GC concentrations and action in adipose tissue. Here, we tested the hypothesis that ABCC1, which i...

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...

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...

Serum was collected with ethical approval from Vanderbilt Medical Center, USA for blinded analysis between clinical phenotypes; heritable and idiopathic PAH patients (hPAH n=13, 14; iPAH n=7, 12) compared to non-PAH control (n =17, 17) (female, males, respectively). Quantification of circulating estrogens in human bio-fluids may reveal insights into disease aetiology but has been hampered through inadequate sensitivity and specificity of immunoassays...