Endocrine Abstracts

Background: 5α-reductase 1 (5αR1) metabolises steroids such as glucocorticoids and androgens, and is highly expressed in murine liver. Genetic disruption of 5αR1 leads to adverse metabolic changes in mice. We hypothesised that dutasteride, a 5αR inhibitor, induces insulin resistance in mice, as in humans, and this effect is underpinned by increased hepatic glucocorticoid action; an experimental paradigm was set up using A-348441, a liver-selective glucocort...

Human plasma contains both cortisol (F) and corticosterone (B). B has been largely neglected in humans as it is 10–20 times less abundant however previous studies suggest B and F have differential tissue-specific actions. Compared with F, B has an enhanced response to ACTH, relatively higher concentrations in brain and CSF and differential transmembrane trafficking by ATP-binding cassette (ABC) transporters. Plasma F is bound to corticosteroid-binding globulin (CBG) and a...

Background: Using a deuterated tracer (D4-cortisol) to measure cortisol regeneration from cortisone in vivo we have quantified tissue-specific 11βHSD1 activity in health and disease, and acute regulation eg by insulin. These studies relied on tracer enrichment in the total plasma cortisol pool, assuming rapid equilibration between free and protein-bound pools. Slower equilibration would result in underestimation of enzyme activity, and has implications for the co...

Introduction: Adrenal insufficiency is rare in the neonatal period and if unrecognised may cause life-threatening circulatory collapse. The initial investigations taken at the time of presentation, and prior to the institution of hydrocortisone, are a key step in the diagnostic pathway, and aid the clinician to distinguish adrenal insufficiency from mineralocorticoid resistance or renal tubulopathy. A cortisol measurement at the time of illness is useful to evaluate the adrena...

5α-Reductase (5αR) inhibitors decrease prostatic dihydrotestosterone in benign prostatic hyperplasia (BPH) treatment; finasteride inhibits 5αR type 2, while dutasteride inhibits 5αR1 and 2. 5αRs, especially 5αR1, are also expressed in metabolic tissues regulating actions of androgens and other substrates, including glucocorticoids.Hypothesis: 5αR1 inhibition with dutasteride induces metabolic dyshomeostasis.<p class...

5α-Reductase 1 (5aR1) catalyses A-ring reduction of glucocorticoids and androgens, predominantly in liver and modulates steroid hormone action. We previously demonstrated transgenic disruption of 5aR1 predisposes mice to developing fatty liver. Here we tested whether 5aR1 disruption increases susceptibility to the development of liver injury, using the carbon tetrachloride induced liver fibrosis model.Male 5aR1−/− (KO) mice and wild-type...

Background: Several devices are available for the administration of recombinant GH. A prospective study was undertaken to look at those attributes of GH delivery device most important to patients when making their choice.Objectives: i) To understand which features of a GH device are considered most important to patients when choosing a device. ii) Comparison of patient’s device preferences at start of GH treatment and after 2 years of treatment. iii...

UK National Acromegaly Register collects data on real-life clinical practice in 34 centres. We analysed all GH and IGF1 data to assess adequacy of control on medical treatment (Rx) with somatostatin analogs (SMS) and dopamine agonists (DA).Methods: All GH records (basal, profile or GTT) in database were correlated with IGF1, Rx, surgery (TSS) and radiotherapy (RT), then processed to derive summary data for each patient and each course of Rx. GH considere...

Tissue cortisol levels are amplified by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In mice, transgenic overexpression of 11β-HSD1 causes the metabolic syndrome, consequently 11β-HSD1 inhibitors are a promising therapeutic target. However, determining the importance of 11β-HSD1 in humans has proved more complicated, in part due to difficulty quantifying in vivo activity. We hypothesized that cortisol regeneration by 11β-H...

UK National Acromegaly Register collects data on routine clinical practice in 34 centres. We analysed all GH and IGF1 data to assess adequacy of control & responses to medical treatment (Rx) with somatostatin analogs (SMS) & dopamine agonists (DA). Methods: Under program control, GH records (basal, profile or GTT) were correlated with IGF1, tumour size, Rx, surgery (TSS) & radiotherapy (RT) in the database, then processed in Excel to derive summary data for each pa...