Obesity is known to be tied to infertility in women, and a new study suggests a possible reason why: the brain's pituitary gland may be sensitive to the increased insulin levels that occur with obesity, and in turn, may impair fertility.

The study, conducted in mice, shows that high levels of insulin, a hormone that helps control blood sugar, act on the pituitary gland, which is involved in regulating ovulation. Elevated levels of insulin, a side effect of obesity , prompt the pituitary gland to pump out large amounts of hormones that disrupt ovulation.

This effect of insulin on the pituitary gland is different from its effects on other parts of the body, the researchers say. In obese people, cells in the liver and muscle can stop responding to insulin, a state known as insulin resistance , which is linked to Type 2 diabetes. The new study suggests that not all cells in the body become insulin resistant.

"What we propose is a fundamentally new model showing that different tissues respond to obesity differently, and that while cells in the liver and muscle do become insulin resistant, cells in the pituitary remain sensitive to insulin," said study researcher Andrew Wolfe of Johns Hopkins Children's Center in Baltimore.

More research is needed to see whether the findings hold true for humans, the researchers say.

Insulin in the brain

The researchers focused on pituitary cells called gonadotrophs which produce luteinizing hormone, critical for ovulation and fertility.

They engineered mice with missing insulin receptors in their pituitary glands and compared them to mice with intact insulin receptors (cells without insulin receptors cannot receive or respond to the insulin signal).

After three months on a high-fat diet, the obese mice with intact insulin receptors developed all the classic symptoms of polycystic ovary syndrome, a common cause of infertility in women. Some of the mice's symptoms included irregular reproductive cycles and fewer ovulations.

The mice with missing insulin receptors, however, maintained near-normal levels of luteinizing hormone, regular cycles and normal ovulation, despite their obesity.

Impact on pregnancy

To determine whether these hormonal differences would carry over into actual differences in fertility, the researchers allowed the mice to mate. The pregnancy results mirrored the hormonal findings.

Obese mice with missing pituitary insulin receptors had near-normal pregnancy rates, with five times more successful pregnancies than obese mice whose pituitary insulin receptors were intact.

The study will be published online Sept. 8 in the journal Cell Metabolism.