Role of Progesterone in the Etiology of Breast Cancer.

One of our research goals is to examine the effects of age on mammary development analogous to that accompanying pregnancy and determine if this differs between normal mice and mice carrying an imbalance in the natural ratio of the two forms A and B forms of progesterone receptor progesterone receptor is essential for pregnancy dependent mammary development. Our studies conducted during the past grant period reveal that with increasing age mammary glands acquire a greater sensitivity to estrogen and progesterone, which becomes dramatically evident at approx. 8 months of age. This is particularly significant since approx. 8 months of age in mice roughly corresponds to a peri-menopausal human female. This means that in the aging female who is known to be at a higher risk for breast cancer, one of the contributing factors may be an increased sensitivity to sex steroids. We also find that a with increasing parity more epithelial cells are present in maminary glands which, once again, is very dramatic after four pregnancies and b in transgenic mice carrying an excess of the A form of progesterone receptor and hence an imbalance in the normal ratio of the two forms of progesterone receptor, mammary morphogenesis is altered.