Solving an Estrogen Riddle

Until late 1995, researchers could not explain why estrogen, one of the most widely prescribed therapeutic hormones, affects certain tissues in the body, including the bladder and the ovaries. These organs appeared to lack the receptor to which estrogen must bind in order to be effective. The recent finding of a second estrogen receptor opens the door for studies that will increase understanding of estrogen's action, as well as of how certain compounds can have estrogen-like effects in some tissues and inhibit estrogen in others. These studies may lead to improved drugs for breast cancer and for protection against cardiovascular problems, Alzheimer's disease, and osteoporosis.

NIGMS grantee Dr. Thomas Scanlan and his group at the University of California, San Francisco were the first to discover a pathway by which the two receptors respond differently to estrogen; DES, an estrogen-like synthetic compound; and several estrogen-blocking compounds, including the anti-cancer drug tamoxifen.

The knowledge gained from this research may enable scientists to develop therapeutic estrogen-like hormones that would not produce the side effects of current estrogen drugs. For instance, they might be able to develop drugs that would protect against osteoporosis without increasing the risk of uterine cancer. In addition, this work may help researchers determine why tamoxifen sometimes stops working. So far, however, it appears that there are more complexities in the system, because there may be additional forms of the newly found receptor as well as other proteins that interact with the receptors.

REFERENCE

Paech K, Webb P, Kuiper GJM, Nilsson S, Gustafsson JA, Kushner P, Scanlan T. Differential ligand activation of estrogen receptors ER and ER at AP1 sites. Science 1997;277:1508-10.

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