{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n 11β‐hydroxysteroid dehydrogenase type 1 (HSD11B1) is an endoplasmic reticulum–bound enzyme that primarily converts inert cortisone into biologically active cortisol, thereby finely tuning intracellular glucocorticoid levels ("}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "). By acting as an intracellular amplifier of glucocorticoid action, HSD11B1 influences a wide spectrum of physiological processes. In metabolic tissues such as liver, adipose tissue, and bone, its oxoreductase activity—critically supported by NADPH generated via hexose-6-phosphate dehydrogenase—promotes gluconeogenesis, adipocyte differentiation, and bone turnover."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Elevated HSD11B1 expression in adipose depots has been linked to obesity, insulin resistance, and other features of the metabolic syndrome; indeed, genetic and epigenetic variations in the HSD11B1 gene contribute to altered hormonal balance and metabolic dysfunction ("}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "). Furthermore, aberrant HSD11B1 function is implicated in conditions such as cortisone reductase deficiency and has been associated with an elevated risk for neurodegenerative disorders through its impact on intracellular cortisol homeostasis ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ").\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n HSD11B1 is not confined to classical metabolic tissues; its expression in the placenta and in immune cells helps modulate local glucocorticoid action during parturition and inflammatory responses. Environmental factors, such as bisphenol A, can upregulate HSD11B1 in adipocytes, thereby further driving adipogenesis ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "). Moreover, recent evidence demonstrates that epigenetic regulators—for example, the histone demethylase LSD1—can repress HSD11B1 expression in brown adipose tissue to favor mitochondrial oxidative capacity and overall energy expenditure ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ").\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted role of HSD11B1 as a critical regulator of tissue-specific glucocorticoid action. By controlling local cortisol regeneration, HSD11B1 integrates metabolic, inflammatory, and developmental signals, thereby influencing energy homeostasis and representing a promising therapeutic target for metabolic and other glucocorticoid‐related disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nicole Draper, Elizabeth A Walker, Iwona J Bujalska, et al. 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