Dg. Monroe et al., Estrogen opposes the apoptotic effects of bone morphogenetic protein 7 on tissue remodeling, MOL CELL B, 20(13), 2000, pp. 4626-4634
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.