Endocrine Abstracts

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...

Background & Aims: Observational studies implicate glucocorticoid excess, principally due to altered steroid metabolism in target tissues, in both the insulin resistance and liver fat accumulation that accompanies type 2 diabetes. To test the contribution of glucocorticoid signalling to metabolic dysfunction we blocked cortisol secretion (with metyrapone) and action (with the GR antagonist mifepristone) simultaneously in men with type 2 diabetes ± fatty liver.<p c...

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...