Endocrine Abstracts

Background: 5α-Reductase (5αR) catalyses conversion of testosterone to its more potent metabolite dihydrotestosterone (DHT) and is inhibited when treating benign prostatic hyperplasia. 5αR has two isozymes; dual isozyme inhibition with dutasteride gives greater DHT suppression than finasteride, which inhibits only 5αR type 2.Aim: To develop a novel assay to simultaneously analyse testosterone, epitestosterone, DHT, androstenedione, du...

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...

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...

Liquid Chromatography tandem mass spectrometry (LC–MS/MS) is gold-standard for androgen analysis in biological fluids, superseding immunoassays in specificity, particularly at low concentrations. While LC–MS/MS is well established for analysis of testosterone (T) and androstenedione (A4), 5α-dihydrotestosterone (DHT) presents greater analytical challenges. DHT circulates at low nanomolar concentrations in men and lower in women, ionising inefficiently. Thus, eve...

Non-invasive methods to measure enzyme activity in vivo can provide a useful tool for the development of selective inhibitors. Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), a reductase enzyme that amplifies active intracellular glucocorticoid levels, has been shown in obese patients using invasive tools (biopsy, microdialysis and arteriovenous sampling with stable isotope tracers). 11β-HSD1 inhibitors are efficacious in...