The endometrium is a unique adult tissue which, in the absence of pregnancy or disease, undergoes cyclic breakdown and regrowth approximately 400 times during a woman's reproductive life. The chances of reproductive success during each cycle depends on appropriate, cell-specific responses to steroids, including expression of matrix metalloproteinases (MMPs). Normal endometrial MMP regulation in response to either estrogen or progesterone requires additional, cell-specific interactions mediated by various growth factors and cytokines. During endometrial maturation, progesterone, retinoic acid and TGF-beta act cooperatively, providing a remarkable biological balance to regulate expression of MMPs in the highly steroid-sensitive endometrium. Exploring the regulatory actions of locally produced growth factors and cytokines on members of the MMP family and their inhibitors will allow a better understanding of the unique physiology of the human endometrium under the influence of progesterone.