In contrast, chronic stress may be characterized by hypocortisolemia (insufficient production of cortisol) [46] or epigenetic changes in the placenta, leading to the downregulation of HSD11B2. Although the exact mechanism between maternal distress and downregulation of HSD11B2 is unknown [21], elevations in proinflammatory cytokines [47,48], stimulation of the sympathoadrenal system [49] and DNA methylation [21] have been implicated. Here, HSD11B2 is linked to adrenocortical insufficiency.