Anne-Sophie Koning

My main research project is a clinical trial in which we try to prevent neuropsychiatric adverse effects of the synthetic glucocorticoid dexamethasone. The naturally produced hormone cortisol acts on both the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), whereas dexamethasone mainly activates GR with low or absent binding to the MR. Dexamethasone strongly suppresses endogenous cortisol production through GR-mediated negative feedback mechanisms in the hypothalamus-pituitary-adrenal (HPA) axis, leaving the MR empty and not activated. This had led to the hypothesis that, in addition to the strongly stimulated GR, reduced MR activity may underlie the neuropsychiatric adverse effects of dexamethasone. We hypothesize that increasing MR activity with physiological doses of cortisol may prevent or diminish the disrupting neuropsychiatric effects in patients treated with dexamethasone. In our clinical trial we include brain tumour patients, because they receive high doses of dexamethasone perioperatively.

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