Published by the Students of Johns Hopkins since 1896
January 28, 2022

Increased insulin levels may induce infertility

By Mali Wiederkehr | September 23, 2010

A recent study by the Hopkins Children’s Center reveals the mechanism that puts obese women at a higher risk for infertility.

The study found that the pituitary gland responds to chronic high levels of insulin in a way that hormonally impedes fertility. Obesity is almost always linked to high levels of insulin.

In order to test that the pituitary gland’s sensitivity to high levels of insulin interferes with fertility, Hopkins researchers created a study using mice. They focused on special cells in the pituitary gland known as gonadotrophs, which produce hormones that control fertility. One of the more familiar hormones that these cells produce is luteinizing hormone, or LH.

The researchers genetically engineered mice that lacked insulin receptors in the gonadotrophs. They kept one group of these mice lean and healthy, and fed the other group highly fatty foods for three months.

They also kept control groups of lean mice and normal obese mice with normally functioning insulin receptors.

In order to test reproductive success, the researchers mated the mice. They found that lean mice, whether lacking insulin receptors or with normal receptors, had six times the number of successful pregnancies as obese mice with normal insulin receptors.

Obese mice lacking insulin receptors had five times the number of successful pregnancies as obese mice with functioning receptors. They also had standard reproductive cycles and almost standard hormone levels. This experiment illustrated that removing the insulin receptors dramatically increases fertility in obese mice.

The obese mice with normal receptors were infertile, and had symptoms that resembled a human condition known as polycystic ovarian syndrome (PCOS). PCOS is the most common form of infertility, affecting one in 10 women, and is caused by many small ovarian cysts.

This new model for understanding infertility risk in obesity could potentially give rise to new treatments for PCOS, as well as other forms of infertility.

The majority of previous obesity and insulin studies have mostly focused on metabolic tissues, meaning tissues concerning the metabolism. This makes sense, for obesity has much to do with the metabolism. Some of the tissues explored in previous studies include the liver, fat and muscle.

"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," principal investigator Andrew Wolfe, of the Hopkins Children’s Center, was quoted as saying in a press release.

This study contradicts the previously held belief that infertility is caused by insulin resistance. Insulin resistance occurs when cells become insensitive to chronic high levels of insulin. Insulin resistance is found in metabolic cells in an obese person, but not in cells of the pituitary gland.

Wolfe is interested in uncovering the trait that allows pituitary gland cells to remain sensitive to insulin even after metabolic cells become insensitive.

This study will hopefully become the kickoff point for exploring obesity and insulin in more than just metabolic tissues.

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