Infertility in women is often linked to obesity. A new study published in Cell Metabolism suggests that insulin signalling in the pituitary gland could play a key role.
Obese individuals can also sometimes be insulin resistant (IR), with tissues and organs such as the liver, fat and muscle being affected. Insulin resistance is closely linked to conditions such as type II diabetes, and is also thought to play an important part in infertility.
Previous work carried out by the group based at the Johns Hopkins Children's Centre found that the pituitary gland - a region of the brain involved in the regulation of hormones - contains many insulin receptors.
In their new study, the researchers set out to see if cells in the pituitary gland were IR and whether this contributed to infertility. They created mice that lacked these pituitary insulin receptors, and surmised that if IR was the link between obesity and infertility, the mice lacking the insulin receptors should be infertile. However, to their surprise, these mice had normal fertility.
The researchers then went on to assess the effect of insulin signalling in obesity, by feeding the mice an unhealthy, high-fat diet for three months. Whereas normal obese mice became infertile and had abnormal reproductive hormone levels, the mice without the receptors had normal reproductive function and near-normal hormone levels.
The authors concluded that these findings show that, firstly the pituitary gland remains sensitive to insulin, and secondly when there are high levels of insulin, as occurs in obesity, this sets off a hormonal chain reaction which leads to infertility.
Professor Andrew Wolfe, who led the study, said 'There was a sense that the reproductive dysfunction was due to insulin resistance', however, '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'.
Doctors have traditionally focused on lowering insulin resistance as a way of treating infertility. But this new model suggests that decreasing the pituitary glands sensitivity to insulin could be an important new target for treatment instead.