Early puberty can lead to health problems later in life

Mengjie Wang is a PhD graduate student at the University of Toledo College of Medicine and Life Sciences biomedical science program.

We all go through puberty, the period of time when children physically and emotionally develop into young adults. Puberty happens when a part of the brain called the hypothalamus tells the body to release male or female hormones. In response, height and weight increase, and male or female characteristics begin to develop.

Puberty is considered early if it occurs before a girl is 8 years old or a boy is 9 years old. Around the world, puberty is starting earlier than it once did. Today, about one in 5,000 children goes through early puberty. The known risks for these children can include childhood bullying for body changes, short adult height, and an increased risk of breast cancer.

A clearer understanding of all risks of early puberty is important to patients and physicians.

Central precocious puberty is a common type of early puberty that involves your hypothalamus. In most cases, we don't yet know what causes this, but brain tumors, injury, or inflammation are some of the causes.

A child going through puberty needs enough energy to have normal development. An obese child actually provides more energy than the child needs for normal development. This extra energy sends incorrect signals to the hypothalamus for puberty to start. Obesity and early puberty are serious health issues in the United States.

I study how the hypothalamus part of your brain controls obesity, puberty, and reproduction in our lab at the University of Toledo College of Medicine and Life Sciences, formerly the Medical College of Ohio.

We overfed female mouse models by giving them high-fat- diets from the day they deliver their pups until weaning (21 days) to investigate the potential effects of obesity and overfeeding in breastfeeding mothers. Surprisingly, we found that overfeeding the mothers during breastfeeding can cause obesity in the pups and significantly advance the start of their puberty.

This is the first evidence showing that overfeeding during breastfeeding influences obesity and puberty in the offspring.

Does early puberty, caused by overfeeding, also cause other health problems? We did glucose (sugar) tolerance tests and insulin tolerance tests to determine if these pups would develop diabetes when they became adults at 3 months old. We measured blood glucose levels every 15 minutes after giving them a large dose of sugar. Surprisingly, we found that these overfed mice could not keep their glucose levels within normal range. After we gave them insulin, which usually lowers blood glucose, their blood glucose measure did not fall.

These results show that overfed mice from overfed mothers are glucose intolerant and insulin insensitive. This means that obese mice with early puberty also have increased risk of developing diabetes during adulthood.

We then performed a fertility test on the obese mice when they were 4 months old. This tests the adults’ ability to reproduce. Notably, these experiments showed that female mice have trouble getting pregnant and have fewer pups than normal. Therefore, our studies also show evidence that obesity-induced early puberty can also contribute to reproductive problems during adulthood.

Another important player in the effects of childhood obesity is something called Insulin-like growth factor-1 (IGF-1). This is a protein secreted from the liver that regulates body growth and puberty. The hypothalamus in your brain can sense changes in IGF-1 levels and provides feedback signals to regulate IGF-1. We know that there are specific cells in the hypothalamus, called leptin-responsive cells that have IGF-1 receptors. This means that these specific cells can receive signals from IGF-1.

We used research methods to delete the IGF- 1 receptors in those leptin-responsive cells in the hypothalamus and then we tested these mice. We discovered that loss of IGF-1 receptors in otherwise normal mice will cause decreased body weight, along with delayed puberty and reproductive problems. This is the first evidence that IGF-1 receptors in leptin-responsive cells in the brain is important to normal body weight, puberty, and reproduction.

Doctors don’t always follow the same patients from puberty to adult life. Therefore our findings can alert doctors and patients with early puberty that other health problems may arise after they become adults. Correct treatment and follow-up are both important for patients with early puberty.

Mengjie Wang is a PhD graduate student at the University of Toledo College of Medicine and Life Sciences biomedical science program. She is completing her doctoral studies in the Molecular Medicine track in the lab of Jennifer Hill. For details, email Mengjie.Wang@rockets.utoledo.edu or go to utoledo.edu/​med/​grad/​biomedical.