Changing the sugars attached to a hormone produced in the pituitary gland increased fertility levels in mice nearly 50 percent, School of Medicine research has found. The change appears to alter a reproductive thermostat, unveiling part of an intricate regulatory system that may eventually 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,” said the research group’s leader, Jacques Baenziger, M.D., Ph.D., professor of pathology & 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.
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.
Baenziger said the researchers didn’t notice much change in the animals initially. But 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,” Baenziger said.
“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.”