Moved to clinical practice, this model helps to understand that, in adrenal insufficiency, loss of GC feedback, by itself, can increase POMC gene expression in the pituitary (suggesting that CRH is not absolutely required for changes in POMC expression in response to absolute GC deficiency), but CRH action is essential to guarantee the increase of ACTH secretion. The gene discussed is CRH; the disease is Adrenal insufficiency.