Glucocorticoids regulate corticotropin-releasing hormone (CRH) gene expression in the placenta and the brain. In both the placenta and two extrahypothalamic sites in the brain (the amygdala and the bed nucleus of the stria terminalis), glucocorticoids elevate CRH gene expression. One functional role of the elevation of CRH by glucocorticoids may be to signal adversity. When CRH is over-expressed in the placenta, it may indicate that the pregnancy is in danger, and preterm labor may result. When CRH is over-expressed in the brains of animals, they may become more fearful. Both situations possibly reflect allostatic mechanisms and vulnerability to allostatic overload, a condition in which biological tissue may be compromised.