'Catch-up' growth signals revealed

Jan 27, 2011

(PhysOrg.com) -- University of Michigan researchers have uncovered molecular signals that regulate catch-up growth -- the growth spurt that occurs when normal conditions are restored after a fetus, young animal or child has been ill, under stress or deprived of enough food or oxygen to grow properly.

The results, published in the Feb. 15 issue of the journal Development, could lead to better understanding of why babies who undergo catch-up growth are at higher risk in later life for diabetes, , and other health problems.

"Catch-up growth is a widespread phenomenon in the animal kingdom, from humans down to little fish and ," said Cunming Duan, U-M professor of molecular, cellular and developmental biology. "But biologists have known very little about the molecular signals that coordinate this phenomenon."

Duan and co-workers suspected that a group of hormones called insulin-like growth factors (IGFs)—known to be important in normal growth and development and also implicated in cancer and aging—might be involved. Like other peptide and protein hormones, IGFs work by binding to receptors on the cells they target. The binding then sets off a cascade of reactions that ultimately direct the cell to do something.

"Since we were dealing with a type of growth, it made sense to look at the main growth regulators," Duan said.

Also, in research published in 2010, Duan's group found that altering levels in muscle cells changed the chemical signal of IGF. Knowing that catch-up growth can be triggered by changing oxygen levels, the researchers reasoned that IGF might mediate the process.

Using zebrafish as a model system, Duan's group did a series of experiments. First, they simply monitored growth and IGF signaling in fish embryos grown in water in which the oxygen concentration was reduced for a time and then restored. As expected, growth was suppressed when oxygen was low, but the fish caught up with a growth spurt when oxygen was restored to normal levels. Interestingly, IGF signals changed in concert with oxygen levels.

Next the researchers repeated the low-oxygen, normal-oxygen experiment with a different twist: They blocked IGF signaling in the fish embryos, using either genetic methods or pharmacological inhibitors.

"We found that if you block IGF signaling, the animal cannot catch up," Duan said. "From this we learned that the IGF signal is not only changing, but that the change is really necessary for the animal to catch up."

Duan's group went on to investigate the specific biochemical pathways involved. They found that one, called the MAP kinase pathway, is critical for catch-up growth. However, it may not be the only pathway that figures in, and the specific pathway used may depend on circumstances.

"You can think of it like your route to work. Maybe you normally take I-94, but if it's blocked, you use other routes that you normally don't use," Duan said.

In future research, Duan's group wants to explore the long-term effects of changes in the IGF-MAP kinase pathway that are related to catch-up growth.

"If we find lasting changes, we may be able to figure out ways of intervening to reduce the risk of associated that develop later in life," Duan said.

In addition to Duan, the paper's authors are postdoctoral fellow Hiroyasu Kamei, former postdoctoral fellow Yonghe Ding, former graduate student Shingo Kajimura, graduate student Michael Wells and former undergraduate student Peter Chiang.

Explore further: Students create microbe to weaken superbug

More information: dev.biologists.org/

Related Stories

Researchers solve a molecular mystery in muscle

Mar 15, 2010

The muscle-building abilities of hormones known as insulin-like growth factors (IGFs) are legendary. Just do an online search and you'll find not only scientific papers discussing the effects of IGFs on the cells that give ...

New molecular therapy candidates for pancreatic cancer

Apr 19, 2010

A research team from Japan investigated expression of insulin-like growth factor-I receptor (IGF-IR) in pancreatic cancer cell lines. All the cell lines examined expressed IGF-IR under culture conditions without IGF-I in ...

Hormone may hold key to helping elderly men live longer

May 27, 2008

Elderly men with higher activity of the hormone IGF-1—or insulin-growth factor 1—appear to have greater life expectancy and reduced cardiovascular risk, according to a new study accepted for publication in the Journal of ...

Low levels of key protein may indicate pancreatic cancer risk

Aug 15, 2007

A protein that dwindles in response to obesity and a sedentary lifestyle may one day help doctors predict which people are at increased risk for pancreatic cancer, new research by Dana-Farber Cancer Institute and collaborating ...

Recommended for you

How calcium regulates mitochondrial carrier proteins

9 hours ago

Mitochondrial carriers are a family of proteins that play the key role of transporting a chemically diverse range of molecules across the inner mitochondrial membrane. Mitochondrial aspartate/glutamate carriers are part of ...

Precise measurements of microbial ecosystems

10 hours ago

The Luxembourg Centre for Systems Biomedicine (LCSB) has succeeded for the first time in describing the complex relationships within an ecosystem in unprecedented detail. For their work, carried out in collaboration ...

Students create microbe to weaken superbug

21 hours ago

A team of undergraduate students from the University of Waterloo have designed a synthetic organism that may one day help doctors treat MRSA, an antibiotic-resistant superbug.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.