Hormones Dictate Types of Proteins Cells Produce, Study Shows Future Drugs May Change “Wrong” Proteins to “Right”

Naturally occurring hormones such as estrogen, progesterone and cortisol play an important role in determining what kind of protein cells make in response to a genetic message, said researchers at Baylor College of Medicine in last month’s issue of the journal Science.

“These steroid hormones can change the protein that comes from a gene,” said Bert O’Malley, M.D., chairman of cellular and molecular biology at Baylor and senior author of the paper.

When a gene is activated, its DNA is transcribed or translated into messenger RNA, which carries the message about which protein is to be made to the assembly apparatus of the cell. However, one gene can produce different kinds of messenger RNAs, resulting in different proteins. The process is called “alternative splicing.”

“This explains how 30,000 human genes can result in more than 100,000 proteins,”O’Malley said.

O’Malley and his colleagues found that hormones achieve this effect by binding to their specific receptors in the cell. The receptors then find the appropriate genes and recruit a specific set of molecules called “co-activators.” These co-activators then find splicing factors that govern which portions of the gene are included in the messenger RNA. The message the RNA carries determine the kind of protein that is made.

The co-activators can both change the amount of the gene’s message and also change the protein it causes to be produced.

“It points out the tremendous power of hormones,” said O’Malley. “Maybe when hormones do bad or good, it is not because they make too much or too little of a protein but because they make the wrong kind of protein. This could relate to anything from cardiovascular disease to cancer.”

It might be possible to make a drug that could change the type of protein coming off a certain gene, he said. Although such discoveries are far in the future, he said drug companies are already considering the possibility in a variety of areas.

The study’s other authors include Susan Berget, Ph.D., interim chairman of the department of pharmacology at Baylor; Dider Auboef, Ph.D., instructor in cell biology; and Arnd Honig, Ph.D., of the University of Tubingen in Germany.

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©2006 Texas Medical Center

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