Disabling mouse enzyme increases fertility

"To adjust for the right amount of key reproductive hormones such as estrogen and testosterone, we may someday alter the sugars that are added to this hormone or others like it," says the group's leader, Jacques Baenziger, M.D., Ph.D., professor of pathology and immunology and of cell biology and physiology.

The report appeared recently in The Journal of Clinical Investigation.

Sugars are the most common addition to hormones and other proteins after they have been assembled from instructions in DNA. Nearly all proteins in the blood and on the surface of cells have sugars attached. Scientists believe sugar attachments modify and adapt proteins, enabling them to fill more than one job or changing the way they do their jobs in different contexts. But direct demonstration of such changes has been challenging.

Baenziger found a unique set of sugars consistently added to luteinizing hormone, which is part of a feedback loop between the pituitary, the reproductive organs and the liver. The loop cycles up and down over time, producing periodic peaks in other reproductive hormones and triggering regular events such as the ovaries' release of eggs.

For their study, Baenziger's laboratory genetically disabled one of the enzymes that attaches sugars to luteinizing hormone in mice. This enzyme isn't the only one to add sugars to the hormone, so the alteration changes the mix of sugars rather than eliminating them completely.

“Initially, we didn’t seem to see much of a difference in the animals,” Baenziger says. “But then someone came to me and said, ‘We have too many animals. We’re constantly weaning mice!’”

A closer look showed that the mice were having nearly 50 percent more pups than normal, and that the liver removed the altered hormone from the blood more slowly. In addition, female mice were maturing earlier, were always receptive to male overtures for mating and had a disrupted ovulatory cycle. Males had higher levels of testosterone and females had higher levels of estrogen. Surprisingly, the altered female mice were also better mothers: They ate their pups less often.

"One could speculate that fertility problems in some humans may be partly related to a defect somewhere in this very complicated regulatory system," says Baenziger. "They may have the wrong proportion of some of these sugars, or the receptors that clear the sugar-hormone combination from the blood might not bind as well."

Baenziger, who recently won a five-year, $3.3 million grant renewal from the National Cancer Institute, wants to learn more about the segments in the reproductive hormones that single them out for the addition of unique sugars. He hopes to use that information to search for other proteins that receive similar treatment.

"We know these systems for adding sugars are well-regulated, but we're just starting to get a sense for how they are controlled and how far-reaching their effects can be," he says. "I think we're going to see much more of this kind of alteration and regulation of protein properties via added sugars in many other important areas of biology."

Source: Washington University School of Medicine

Killer carbs -- Monash scientist finds the key to overeating as we age
A Monash University scientist has discovered key appetite control cells in the human brain degenerate over time, causing increased hunger and potentially weight-gain as we grow older.
Pheromones enhance sex, slow aging -- in worms
(PhysOrg.com) -- People will pay big bucks for pills that promise to enhance sex or slow aging. Now, a Cornell researcher and colleagues have uncovered a class of small molecules in tiny worms that not only attract mates but also arrest development for months in larvae.
Diabetes linked to male infertility; excess sugars in the body have direct effect on sperm quality
Diabetes in men has a direct effect on fertility, a scientist told the 24th annual conference of the European Society of Human Reproduction and Embryology today. Dr. Con Mallidis from Queen's University, Belfast, UK, said that, despite the prevailing view that it had little effect on male reproductive function, the Belfast group had shown that diabetes caused DNA damage in sperm.
Gene oppositely controlled by dietary protein, sugar
Researchers have discovered a gene in flies whose activity rises and falls depending upon the amount of protein and sugar in the insects’ diets. The findings, reported in the April issue of Cell Metabolism, might shed light on the way the insects’ bodies—and perhaps those of humans too—handle dietary extremes, including high-protein, low-carb diets like the Atkins, according to the researchers. These findings are also yielding new clues about the links between diet and life span.
Insects take a bigger bite out of plants in a higher CO2 world
Atmospheric carbon dioxide levels are rising at an alarming rate, and new research indicates that soybean plant defenses go down as CO₂ goes up. Elevated CO₂ impairs a key component of the plant’s defenses against leaf-eating insects, according to the report. The University of Illinois study appears this week online in the Proceedings of the National Academy of Sciences.
A gene divided reveals the details of natural selection
In a molecular tour de force, researchers at the University of Wisconsin-Madison have provided an exquisitely detailed picture of natural selection as it occurs at the genetic level.
Smart insulin nanostructures pass feasibility test
Biomedical engineers at The University of Texas School of Health Information Sciences at Houston have announced pre-clinical test results in the September issue of the International Journal of Nanomedicine demonstrating the feasibility of a smart particle insulin release system that detects spikes in glucose or blood sugar levels and releases insulin to counteract them.
Your gut has taste receptors
Researchers in the Department of Neuroscience at Mount Sinai School of Medicine have identified taste receptors in the human intestines. The taste receptor T1R3 and the taste G protein gustducin are critical to sweet taste in the tongue. Research now shows these two sweet-sensing proteins are also expressed in specialized taste cells of the gut where they sense glucose within the intestine.

Disabling mouse enzyme increases fertility

Related stories:

News discussion: