Disabling enzyme raises fertility levels by 50pc in mice

Washington, May 17: Scientists at Washington University School of Medicine in St. Louis have achieved about 50 per cent rise in fertility levels in mice by changing the sugars attached to a hormone produced in the pituitary gland.

The researchers say that the change seems 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 oestrogen and testosterone, we may someday alter the sugars that are added to this hormone or others like it," says lead researcher Jacques Baenziger, professor of Pathology and Immunology and of Cell Biology and Physiology.

A research article describing the study, published in The Journal of Clinical Investigation, says that sugars are the most common addition to hormones and other proteins after they have been assembled from instructions in DNA.

The article further says that nearly all proteins in the blood and on the surface of cells have sugars attached.

It is believed that sugar attachments modify and adapt proteins to change the way they perform their jobs in different contexts, though direct demonstration of such changes has been challenging, the article adds.

Baenziger and his colleagues 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.

According to them, the loop cycles up and down over time, producing periodic peaks in other reproductive hormones and triggering regular events like the ovaries' release of eggs.

During the study, the researchers genetically disabled one of the enzymes that attaches sugars to luteinizing hormone in mice, and thereby changed the mix of sugars.

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

Upon a close examination of the mice, the researchers observed that the animals were having about 50 per cent more pups than normal, and that the liver removed the altered hormone from the blood more slowly.

They also found that female mice were maturing earlier, were always receptive to male overtures for mating, and had a disrupted ovulatory cycle.

Besides this, male mice had higher levels of testosterone and females had higher levels of oestrogen.

Surprisingly, the altered female mice were also better mothers, for 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. 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," says Baenziger.

Baenziger wants to learn more about the segments in the reproductive hormones that single them out for the addition of unique sugars, and 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. 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," he says.


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