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Scientists Isolate Sex Hormone That May Control Female Cancers

June 5, 1986

BOSTON (AP) _ Scientists have isolated an elusive hormone that helps control whether fetuses grow to become boys or girls, and they say it may provide a new tool for curing female reproductive cancers.

Researchers said Thursday that they have tracked down the gene that regulates production of the hormone, called Mullerian inhibiting substance, so that it can be mass-produced.

The effort represents another successful attempt by biotechnology to manufacture rare human hormones outside the body for the treatment of disease. But like most of the other hormones concocted this way, its ultimate usefulness in taming human ills still is unclear.

However, if it works as researchers hope, the substance will suppress or cure cancers of the ovaries, cervix, uterine lining, Fallopian tubes and vagina. These cancers kill about 22,000 U.S. women each year.

Dr. Patricia K. Donahoe of Massachusetts General Hospital said she hopes that Mullerian inhibiting substance, or MIS, will be ″a highly selective chemotherapeutic agent that won’t cause toxicity in other cells.″

Human testing could begin in two years, she said. Until then, the material will not be available for even experimental use in the treatment of women with cancer.

A report on the work, conducted by Donahoe and Dr. Richard Cate of Biogen, will be published in Friday’s issue of the journal Cell.

Early in their development, all fetuses have two tubes that are the forerunners of sex organs. One, the Wolffian duct, develops into male sex organs, while the other, the Mullerian duct, becomes female organs.

Male fetuses produce MIS, but females at this stage do not. As its name implies, the hormone makes the Mullerian duct shrink and disappear. And with another hormone, testosterone, the male fetus goes on to grow male sex organs based on the Wolffian duct.

Women’s sex organs develop from the Mullerian duct. Scientists reasoned that a hormone that inhibits the growth of this duct might also stop cancers of the adult organs that are derived from the duct.

Until now, however, this theory has been hard to test, because researchers haven’t been able to acquire the hormone in quantities large enough for experiments. Boys stop making MIS between ages 2 and 6. For reasons that scientists don’t understand, girls begin producing the hormone in minuscule amounts during puberty and continue throughout their adult lives.

Researchers have obtained small amounts of the hormone from calves and tested it against human cancers in test tubes. There it effectively stops the cancers from growing. They have not yet tested the very similar human hormone this way.

″The expectation is that if the bovine (cow) material worked against human tumors, the human material ought to work, if anything, better,″ said Dr. Arlen Fuller, another Massachusetts General researcher.

Much testing remains, however, and even if MIS proves effective against cancer, Biogen officials predicted it won’t be approved for routine human use for five or six years.

Finding ways to control cancer has been a major goal of gene splicing. Alpha interferon, another human hormone produced with this technique, was approved Wednesday for use against a rare form of leukemia.

However, most of the hormones manufactured so far work by boosting the body’s natural immune defenses against disease. MIS is unique because it is targeted against one specific form of tissue.

The researchers speculate that MIS will zero in on reproductive tissue and stop its growth but not harm other organs throughout the body.

Donahoe said MIS also might be useful as a birth control drug. However, there is no evidence that the substance could be used to pick a baby’s sex.

The Mullerian duct is named for Johannes P. Muller, a German anatomist who first described the structure during the 1800s.

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