Estrogen opposes the apoptotic effects of bone morphogenetic protein 7 on tissue remodeling

Interactions between estrogen and growth factor signaling pathways at the l evel of gene expression play important roles in the function of reproductiv e tissues. For example, estrogen regulates transforming growth factor beta (TGF beta) in the uterus during the proliferative phase of the mammalian re productive cycle. Bone morphogenetic protein 7 (BMP-7), a member of the TGF beta superfamily, is also involved in the development and function of repr oductive tissues. However, relatively few studies have addressed the expres sion of BMP-7 in reproductive tissues, and the role of BMP-7 remains unclea r. As part of an ongoing effort to understand how estrogen represses gene e xpression and to study its interactions with other signaling pathways, chic k BMP-7 (cBMP-7) was cloned. cBMP-7 mRNA levels are repressed threefold wit hin 8 h following estrogen treatment in the chick oviduct, an extremely est rogen-responsive reproductive tissue. This regulation occurs at the transcr iptional level. Estrogen has a protective role in many tissues, and withdra wal from estrogen often leads to tissue regression; however, the mechanisms mediating regression of the oviduct remain unknown. Terminal transferase-m ediated end-labeling and DNA laddering assays demonstrated that regression of the oviduct during estrogen withdrawal involves apoptosis, which is a no vel observation. cBMP-7 mRNA levels during estrogen withdrawal increase con currently with the apoptotic index of the oviduct. Furthermore, addition of purified BMP-7 induces apoptosis in primary oviduct cells. This report dem onstrates that the function of BMP-7 in the oviduct involves the induction of apoptosis and that estrogen plays an important role in opposing this fun ction.