International audience; Glucocorticoid hormone metabolism and action are regulated by the 11-beta hydroxysteroid dehydrogenase (11bHSD) isozymes: the 11bHSD2, mostly expressed in the distal nephron, converts cortisol [F] into cortisone [E] in humans or corticosterone [B] into 11-dehydrocorticosterone [A] in rodents (11-dehydro derivatives being inactive compounds), and the 11bHSD1, ubiquitously expressed but abundant in the liver, catalyzes the opposite reaction. Under pathophysiological conditions of severe hypothyroidism, altered glucocorticoid metabolism has been observed, with decreased [F] to [E] conversion 1,2. However, direct functional relationship between these two hormonal pathways has never been demonstrated to date. Using bioinformatics analyses, we identified five thyroid hormone response elements in the promoter region of the murine hsd11b2 gene. Therefore, we aimed at investigating whether thyroid hormones (T3) directly regulate expression and/or activity of the 11bHSD2 enzyme. We used three complementary models: human and mouse translational studies and molecular analyses in HEK293T cells and in fully differentiated KC3AC1 cortical collecting duct cells. Children and adults in hypo-or hyperthyroidism status were first compared either to age-and sex-matched euthyroid controls, or to themselves after reaching a euthyroid status. The urinary [E]/[F] ratio measured by LC-MS/MS method, was used as an index of renal 11bHSD2 activity. Interestingly, a 60% decrease in the [E]/[F] ratio was observed in hypothyroid patients, corroborating our hypothesis (p