A missing link from obesity to infertility discovered

WASHINGTON - Scientists have discovered the mechanism responsible for the link between obesity and infertility.

“There was a sense that the reproductive dysfunction was due to insulin resistance,” said Andrew Wolfe of Hopkins Children’s.

“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 become insulin resistant, cells in the pituitary remain sensitive to insulin,” Wolfe added.

Infertility arises when those insulin-sensitive pituitary cells get flooded with the rising insulin levels that are so common in obesity, the new research shows.

The pituitary is a gland found at the base of the brain. Special cells inside the pituitary known as gonadotrophs produce hormones (specifically gonadotropin-releasing hormone and luteinizing hormone, or LH) that control ovulation and fertility.

It appears that insulin overstimulation in those cells sets off a kind of hormonal chain reaction that leads to infertility.

The researchers previously discovered that gonadotrophs harbor insulin receptors, but no one really knew what the effect of insulin on those receptors was.

In the new study, the researchers investigated by creating mice lacking insulin receptors only in the gonadotroph. When healthy and lean, those mice appeared to do just fine. The researchers asked what might happen if they made the mice obese by feeding them an unhealthy, high-fat diet for three months.

Normal obese mice became infertile, as expected, and showed signs of a condition that is known in humans as polycystic ovarian syndrome (PCOS). (PCOS affects as many as one in ten women and is the most common cause of infertility.)

Those symptoms included high LH and testosterone levels, irregular reproductive cycles, and fewer ovulations. But obese mice lacking pituitary insulin receptors maintained normal reproductive cycles and near-normal hormone levels.

To confirm the effects on fertility, the researchers allowed the mice to mate. Lean mice with or without pituitary insulin receptors had six times the number of successful pregnancies compared to otherwise normal obese mice. The obese mice with missing pituitary insulin receptors fared almost as well; they had five times more successful pregnancies than typical obese mice.

The findings are published in the September issue of Cell Metabolism, a Cell Press publication. (ANI)