Estrogen receptors detected in bone cells.

Estrogen receptors detected in bone cells

For years, scientists have known that osteoporosis, or bone loss, parallets decreasing estrogen levels in postmenopausal women. Suspecting that estrogen directly controls the growth of bone, they have looed for estrogen receptors within bone cells, but to no avail. Now, two research teams using highly sensitive detection methods have discovered small numbers of estrogen-binding sites that are probably receptors within the nuclei of bone cells.

By revealing the likely mechanism of how estrogen regulates bone growth, "the findings provide a rationale for treating menopausal women with estrogen to prevent bone loss," says Lawrence Riggs of the Mayor Clinic in Rochester, Minn., who led one of the studies. Bone researcher David Baylink, of the Veterans Memorial Hospital in Loma Linda, Calif., calls the reports "two of the most important discoveries in the field."

In past experiments on breast cancer and uterine cells, researchers have spotted several thousand estrogen receptors per cell. But with improved techniques, the two groups were able to detect even smaller amounts inside bone cells, they report in the July 1 SCIENCE.

Riggs' team added radioactively labeled estrogen to bone cells, then counted how many estrogen molecules bound to sites in the nuclei. Analyzing the cultured human bone cells, Riggs, Erik Eriksen and Thomas Spelsbergy noted a mean of 1,615 estrogen-binding sites per cell.

In a second study, Barry Komm and Mark Haussler, working at the University of Arizona College of Medicine in Tucson, inclubated lysed nuclei of sarcoma cells from rat and human bone with highly radioactive estrogen. They found approximately 200 estroge-binding sites per cell nucleus. They also observed that estrogen enhanced the cells' production of the genetic messages coding for collagen, a mjaor protein of bone.

Although Komm hesitates to call the nuclear binding sites "receptors" without first isolating the actual proteins that make up the binding sites themselves, he says the evidence argues that they are indeed receptors. Presumably, estrogen binds of and then changes the shape of its receptor, enabling it to fit into a special region of the nucleus and thereby on genes controlling bone growth.

Such results would explain why estrogen as a drug has been able to halt bone loss in postmenopausal women. But estrogen therapy may have unwanted effects, such as possible stimulating the growth of certain breast cancers (SN: 5/14/88, p.314). Still, says Baylink, "no drug is more important in the prevention of osteoporosis than estrogen," and by learning how it acts, scientists may be able to create a form of estrogen that works only on the target receptors and with fewer ill effects.