Hormone's role in insects could give insight for cancer treatment

Starvation typically has dire consequences for an organism's growth. In the tobacco hawkmoth, tissues starved during the last stage of larval development stop growing because they lack the proper nutrients.

But new research shows that in the caterpillar of the moth, also known as Manduca sexta, tissues called imaginal discs, which give rise to structures such as the legs and eyes, form and grow despite severe starvation unless a substance called juvenile hormone is present. The hormone inhibits signals needed for imaginal discs to form and develop into their specified organs in the adult moth.

"You can almost think of the imaginal discs as acting like tumors," said James Truman, a University of Washington biology professor. "Without juvenile hormone, the discs can form and grow at the expense of the rest of the animal, but in the presence of the hormone their growth is coordinated with that of the entire insect."

The findings could have implications for anti-cancer agents as well as for understanding the basis of long-term effects of early infant malnutrition.

The husband-wife team of Truman and Lynn Riddiford, also a UW biology professor, discovered the phenomenon, which is described in a paper published in the June 2 edition of the journal Science. Other authors of the paper are Kiyoshi Hiruma of Hirosaki University in Japan; David Champlin of the University of Southern Maine; and two of Champlin's undergraduate students, Paul Allee and Steven MacWhinnie.

Typically, juvenile hormone declines in the last larval stage, allowing imaginal discs to form and begin developing into adult legs, eyes and antennae. Starvation normally causes higher levels of juvenile hormone during the last larval stage. But when the researchers removed glands called the corpora allata, which produce juvenile hormone, imaginal discs developed and grew despite the fact the larvae were being starved, though growth was slower than normal.

The research shows that juvenile hormone can work independent of nutrition to repress the growth of imaginal tissues in insects. That could herald a change in how scientists think when dealing with cancer or other growth-related phenomena, Truman said. Researchers typically tend to think in terms of chemical signals that promote growth, "but we find in insects that they also have a potent hormone that inhibits growth of developing tissues."

"Our paper is something of a wakeup call that there are hormones that repress growth, as well as those that stimulate it, and we should keep an eye out for them in other organisms, including ourselves," he said.

The work also raises questions about what permanent consequences early infant malnutrition might have for humans.

"It should raise our awareness that some early growth processes are coupled to nutrition, and if you uncouple them you can raise very serious developmental problems," Truman said.

Typically, the onset of metamorphosis to the adult tobacco hawkmoth is associated with the loss of juvenile hormone. But the researchers determined there is something else at work. They identified what they called a "metamorphosis initiating factor" that is tied to nutrition. In feeding caterpillars, nutritional cues can trigger the metamorphosis initiating factor, which in turn can allow imaginal discs to form and grow even when juvenile hormone is present.

In addition, while feeding seems to negate the effect of juvenile hormone in the last larval stage, the researchers found that some aspects of subsequent disc growth are still sensitive to juvenile hormone. When larvae that had not been starved were treated with juvenile hormone early in the last stage of development, they did not molt or go through metamorphosis and instead grew to abnormally large sizes. Their development of leg and wing discs was normal for the first two days and then declined.

"We saw a permanent redirecting of what the animal becomes," Riddiford said.