Model of positive (paracrine) and negative (endocrine) feedback between hepatocellular hepcidin and LEC BMPs. The downstream consequences of hepcidin on LEC BMP production are presented as opposing paracrine (clockwise) and endocrine (counterclockwise) regulatory loops. In the paracrine loop, hepcidin blocks or degrades LEC ferroportin and increases LEC iron. Increased LEC iron increases production of BMPs, which upregulate hepatocellular hepcidin. In the endocrine loop hepcidin blocks or degrades ferroportin on duodenal enterocytes and reticuloendothelial macrophages. Iron retention in these cells decreases plasma iron, and thus LEC iron uptake, to attenuate LEC BMP production and hepatocyte hepcidin expression. Green = promoting; red and dashed = attenuating.