Results from our mechanistic animal study suggested that during sepsis-induced critical illness, preserved hypothalamic corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) expression continuously drives pituitary production of POMC, while high circulating levels of free corticosterone suppress the processing of POMC into ACTH and secretion of mature ACTH into the circulation. The gene discussed is CRH; the disease is Sepsis.