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They were first reported in the body and brain 70 years ago, but only recently have they become of interest. 11\u03b2\u2010HSD2 is a dehydrogenase, potently inactivating glucocorticoids. In the kidney, 11\u03b2\u2010HSD2 generates the aldosterone\u2010specificity of intrinsically non\u2010selective mineralocorticoid receptors. 11\u03b2\u2010HSD2 also protects the developing foetal brain and body from premature glucocorticoid exposure, which otherwise engenders the programming of neuropsychiatric and cardio\u2010metabolic disease risks. In the adult CNS, 11\u03b2\u2010HSD2 is confined to a part of the brain stem where it generates aldosterone\u2010specific central control of salt appetite and perhaps blood pressure. 11\u03b2\u2010HSD1 is a reductase, amplifying active glucocorticoid levels within brain cells, notably in the cortex, hippocampus and amygdala, paralleling its metabolic functions in peripheral tissues. 11\u03b2\u2010HSD1 is elevated in the ageing rodent and, less certainly, human forebrain. Transgenic models show this rise contributes to age\u2010related cognitive decline, at least in mice. 11\u03b2\u2010HSD1 inhibition robustly improves memory in healthy and pathological ageing rodent models and is showing initial promising results in phase II studies of healthy elderly people. Larger trials are needed to confirm and clarify the magnitude of effect and define target populations. The next decade will be crucial in determining how this tale ends \u2013 in new treatments or disappointment.<\/jats:p>","DOI":"10.1111\/joim.13741","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:10:04Z","timestamp":1699488604000},"page":"20-37","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["11\u03b2\u2010Hydroxysteroid dehydrogenase and the brain: Not (yet) lost in translation"],"prefix":"10.1111","volume":"295","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-6624","authenticated-orcid":false,"given":"Jonathan","family":"Seckl","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Sciences Queen's Medical Research Institute University of Edinburgh Edinburgh 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