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Study Clarifies Obesity-Infertility Link

US News & World Report,  Sept 8, 2010
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Being obese has long been linked to infertility in females, but researchers may have been wrong about how the link was forged, a new study suggests.

Doctors and scientists have thought that the fertility problems were caused by resistance to the hormone insulin. Chronically high levels of insulin often accompany obesity, eventually making muscles and other tissues impervious to the hormone’s signals.

A new study in mice shows that the pituitary gland, which helps regulate the release of fertility-associated hormones, remains sensitive to insulin. But in obese mice, insulin’s constant signaling to release the fertility hormones leads to an overabundance of those hormones, and consequently infertility, researchers report in the Sept. 8 Cell Metabolism.

The discovery firmly ties metabolism to fertility in an unexpected way and may have implications for treating women with a condition known as polycystic ovary syndrome, which is characterized by abnormal menstrual cycles and is often associated with obesity and type 2 diabetes.

Researchers led by Andrew Wolfe of Johns Hopkins University stumbled upon the discovery when studying mice genetically engineered to lack proteins called insulin receptors that sit on the surface of a cell, latch onto insulin and pass along the hormone’s message to the rest of the cell. The team had engineered the mice so that insulin receptors were missing only from cells in the pituitary, a gland that it is important for regulating many important body functions, including fertility.

Female mice fed a high-fat diet become obese and have a hard time reproducing. But, to the researchers’ surprise, fat females lacking insulin receptors in their pituitary glands remained fertile. The result was unexpected because researchers had thought that removing insulin receptors would have the same effect as had been theorized in obesity—making the pituitary impervious to insulin signals, and thus less able to release two hormones that help regulate ovulation and fertility.

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