New Hormone Found by S.D. Scientists
In the first discovery of its kind in more than 20 years, San Diego scientists have found a new hormone in the human body: a molecule that shows promise in influencing the development of the human embryo, regulation of cholesterol and treatments of cancer, 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--although it may be years before it becomes known whether the new hormone can be used in drugs for patients.
“It’s terribly important,” said Michael Sporn, chief of laboratory chemo-prevention 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 of it, until now they did not realize the hormone was present in the human body.
There are hundreds of hormones in the body. Up to now, scientists have known of only eight fat-soluble steroid hormones. The new molecule represents the ninth, Evans said.
The last time a new human hormone of this class was discovered was the active form of Vitamin D in 1968, he said.
A family of molecules called receptors enables cells to respond to hormones and other chemical messengers. In the human body, there are literally hundreds of different types of receptors that are activated by only one or two messengers, or hormones. These hormones trigger certain events, such as prompting the cell to grow or stop growing. A tumor, for instance, is formed when a cell is instructed to keep growing.
Members of one family of receptors function as gene activators that respond to thyroid, sex and stress hormones. Some of these genes have also been involved in the formations of certain cancers. Armed with 9-cis retinoic acid, scientists hope they might one day create a treatment that will reverse or prevent a tumor from growing.
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 been shown to help prevent recurrence of tumors among 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 will 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.
In 1990, Mangelsdorf discovered one receptor that did not respond to any known hormone. This one, called retinoid X receptor, did show a weak response to Vitamin A, or retinol. And so the sleuthing began. What messenger--hormone--would trigger a reaction?
It took 20,000 chemical tests in three different laboratories in two states to zero in on the molecule, 9-cis retinoic acid. For some observers, Evans’ success in finding the molecule was particularly sweet because he and his team had predicted its existence.
“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 UC San Diego School of Medicine. “The implications are just enormous. It’s really a very important discovery, and it’s a nice discovery for the lab because they predicted it.”
Scientists have long known about all-trans retinoic acid, which is the parent of 9-cis retinoic acid. Since the discovery of Vitamin A, many scientists believed that the vitamin’s sole active derivative was all-trans retinoic acid.
Newly found 9-cis retinoic acid has the same general atomic composition, but its figure is in a different shape. It also has different properties, Evans said.
“Because of this difference, the new molecule is likely to have unique properties,” he 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.”
With these properties, Evans and others believe, the hormone could be incorporated into treatments for a variety of skin diseases, cancers--including leukemia--and regulation of the body’s cholesterol level. But such treatments are years away as scientists now aim to decipher more about the hormone.
“We know these molecules are very important, and as we understand more and more about these hormones in the body, we realize they will be very effective for treating certain diseases,” Heyman said.
“But at this stage,” Evans said, “we are at the beginning of trying to explore its ultimate significance.”
