COX-2–derived PGE2 has been shown to up-regulate aromatase through a cAMP–protein kinase A (PKA) cascade in human breast tissue, and the production of COX-2–derived PGE2 in the breast tissue has been positively correlated with both obesity and breast inflammation in women [50]. Here, PTGS2 is linked to obesity due to melanocortin 4 receptor deficiency.