Such a mechanism would also explain the residual cortisol synthesis leading to the less pronounced systemic glucocorticoid deficiency indicated by measurable expression levels of glucocorticoid-responsive genes pck1 and fkbp5. Furthermore, the amounts of 21-deoxycortisol detected in our mutant larvae are likely to contribute as an additional factor, transactivating the expression of glucocorticoid-responsive genes, as has been demonstrated in vitro (5). Here, FKBP5 is linked to familial glucocorticoid deficiency.