How hunger pangs push back the onset of puberty in mice

The neural circuit responsible for delaying the onset of puberty in underfed mice has been discovered in a study by neuroscientists at RIKEN. The same circuit is expected to play a similar role in humans too.

The study is published in the journal Neuron.

Having offspring places large demands on female mammals, and they need adequate food to be able to bear them. There is a natural mechanism that limits pregnancies during times of food shortages—the onset of puberty is delayed in young, undernourished females. Interestingly, the opposite effect may be at work in women in the developed world today.

“Women today tend to experience puberty earlier than previous generations,” notes Kazunari Miyamichi of the RIKEN Center for Biosystems Dynamics Research (BDR). “This is likely influenced by increased consumption of high-fat, processed foods.”

Conversely, malnourishment or anorexia can push back puberty in girls. But the mechanism that determines the timing of the onset of puberty based on food availability has not previously been well understood.

Now, Miyamichi and Teppei Goto, also of BDR, and their co-workers have uncovered the neural pathways in female mice that connect feelings of hunger with the delayed onset of puberty.

They found that in well-fed mice nearing puberty, neurons in the hypothalamus that produce kisspeptin—a protein that plays a crucial role in regulating reproductive hormones—exhibit pulsatile activity in which hundreds of them fire synchronously and repeatedly. This pulsatile activity became more frequent, the closer a mouse came to puberty.

But in underfed mice, neurons in the arcuate nucleus—a center in the hypothalamus that registers hunger—reduced the frequency of the pulsatile activity, effectively applying the brakes to the onset of puberty.

At first, Miyamichi thought that hormones might act as the go-between between malnutrition and kisspeptin neuron activity. But the response was much too rapid for that.

“A major surprise was the discovery that once food becomes available, the pulsatile activity of kisspeptin neurons recovers remarkably quickly—within just a few hours,” says Miyamichi.

That finding prompted his team to look into fast-acting neural pathways involved in the sensing of hunger and satiety.

It is highly likely that a similar mechanism operates in people too, Miyamichi believes.

“Given the highly conserved nature of the protein-expressing neurons and kisspeptin in the human arcuate nucleus, there’s little reason to doubt that similar mechanisms operate in humans,” he says.

For Miyamichi, this study is just the beginning. “I believe there’s much more to uncover during the juvenile-to-adolescent period—a developmental window that remains relatively underexplored in neuroscience, which has traditionally focused on the adult brain,” he says.