11β-Hydroxysteroid Dehydrogenase Activity in the Brain Does Not Contribute to Systemic Interconversion of Cortisol and Cortisone in Healthy Men

Context and Objective: 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyses regeneration of cortisol in liver, adipose tissue, and skeletal muscle, making a substantial contribution to circulating cortisol as demonstrated in humans by combining stable isotope tracer infusion with arteriovenous sampling. In the brain, 11βHSD1 is a potential therapeutic target implicated in age-associated cognitive dysfunction. We aimed to quantify brain 11βHSD1 activity, both to assess its contribution to systemic cortisol/cortisone turnover and to develop a tool for measuring 11βHSD1 in dementia and following administration of 11βHSD1 inhibitors. Design, Setting, and Participants: With ethical approval and informed consent, 8 healthy men aged 38.1 years (sd 16.5) underwent an ECG-gated phase-contrast magnetic resonance scan to quantify internal jugular vein blood flow and were infused with 1,2 [2H]2-cortisone and 9,11,12,12 [2H]4-cortisol for 3 h before samples were obtained from the internal jugular vein and an ar...