Disabling mouse enzyme increases...( St. Louis May 16 2008 Changing the ...)

St. Louis, May 16, 2008 Changing the sugars attached to a hormone produced in the pituitary gland increased fertility levels in mice nearly 50 percent, a research group at Washington University School of Medicine in St. Louis has found. The change appears to alter a reproductive "thermostat," unveiling part of an intricate regulatory system that may one day be used to enhance human 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 didnt seem to see much of a difference in the animals, Baenziger says. But then someone cam
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