Progesterone Triggers Breast Inflammation

Sandra Z. Haslam, Ph.D., Jian-Wei Xie, Ph.D., Richard J. Miksicek, Ph.D., Susan E. Conrad, Ph.D., and Richard C. Schwartz, Ph.D.,
Michigan State University
NIEHS Grant U01ES012800

NIEHS-funded researchers at Michigan State University report that exposure to the hormone progesterone activates genes that trigger inflammation in the mammary gland. This inflammation may be a key factor in increasing the risk of breast cancer.

Paradoxically, progesterone promotes normal development of the breast, but it has been previously identified as a risk factor for breast cancer. Exposure to progesterone in normal amounts causes breast inflammation which leads to development. Exposure to progesterone in post-menopausal hormone therapy is a known risk factor for breast cancer.

In a laboratory mouse study, the researchers examined genes activated by progesterone and the effects of their activation. They found that progesterone regulates 162 genes in pubertal cells, 104 genes in adult cells and 68 genes in cells during both developmental stages. Some of these genes code for small proteins called chemokines active in the process of inflammation.

The study identified the targets of progesterone receptor A in mammary cell development. These links provide avenues of research and potential therapies in reducing the influence progesterone has on developing breast cancer.

Citation: Santos SJ, Aupperlee MD, Xie J, Durairaj S, Miksicek R, Conrad SE, Leipprandt JR, Tan YS, Schwartz RC, Haslam SZ. Progesterone receptor A-regulated gene expression in mammary organoid cultures. J Steroid Biochem Mol Biol. 2009 Jul;115(3-5):161-72.