SCIENCE GENETICS : Discovery of Another Human Hormone Is First in 20 Years

In the first discovery of its kind in more than 20 years, scientists here have found a new hormone in the human body--one that shows promise in influencing the growth of the human embryo, regulating cholesterol and treating cancers, according to a scientific journal.

“It’s rare to discover new hormonal systems. Historically, they represent major discoveries . . . so we are extremely excited,” said Ron Evans, head of the Gene Expression Laboratory at the Salk Institute and an author of the study published in today’s issue of Cell.

The finding by Evans and his colleagues provides fresh turf in a much-pursued field as researchers grapple with questions about how hormones work, though it may take years before it is known whether the new hormone can be used in drugs for patients.

“It’s terribly important,” said Michael Sporn, chief of laboratory chemoprevention at the National Cancer Institute in Bethesda, Md. “It tells us there are more substances in this whole family of . . . molecules that will be useful in manipulating how cells behave, and that might someday be useful in preventing cancer.”

The new hormone, called 9-cis retinoic acid, is a derivative of vitamin A. While scientists have known that 9-cis retinoic acid exists, they did not before realize that it is present in the human body or what it does there.

Of the hundreds of hormones, scientists have before now only known of eight that are fat-soluble steroid hormones. The new molecule represents the ninth, Evans said.

The last time a new human hormone of this class of steroid hormones was discovered was the active form of vitamin D in 1968, Evans said.

In recent years, scientists have discovered that some patients with certain types of cancer--such as leukemia--respond to treatments using vitamin A. In other studies, vitamin A treatments have helped prevent recurrence of tumors in patients with breast and lung cancers.

“We believe the new molecule, 9-cis, would be a good candidate for treatment of these patients and we intend to test this idea as soon as possible,” said Evans, who predicted that the molecule would be used in a clinical trial within a year.

Since 1985, Evans, David Mangelsdorf of Salk, and Richard Heyman, the senior research manager of Ligand Pharmaceuticals in San Diego, have been working with a family of receptors that recognize chemical messengers and elicit cellular responses to steroid and thyroid hormones.

Receptors are a family of molecules that allow cells to respond to hormones and other such chemical messengers. The human body has literally hundreds of receptors that are activated by only one or two messengers, or hormones. The hormones govern certain events, like cell growth. A tumor, for instance, is formed when a cell is ordered to keep growing. Armed with 9-cis retinoic acid, scientists hope they might one day create a treatment to reverse or stop a tumor from growing.

In 1990, Mangelsdorf discovered one receptor that did not respond to any known hormone. This one, called retinoid X receptor, showed a weak response to vitamin A, or retinol. So the sleuthing began: What messenger--hormone--would trigger a reaction?

It took 20,000 chemical tests in three labs in two states to zero in on the molecule. And Evans and his team had predicted its existence before they found it.

“This is a real triumph. A few years ago, they described a new class of receptors and several years later, they proved the hypothesis,” said Dr. Geoffrey Rosenfeld, an investigator at the Howard Hughes Medical Institute at the UCSD School of Medicine. “The implications are just enormous.”

Because 9-cis retinoic acid is configured slightly differently from its parent molecule, all-transretinoic acid, “the new molecule is likely to have unique properties,” Evans said. “Those properties are likely to include an ability to influence skin growth. It’s also likely to play an important role in vision and bone development.”