Certain chemicals may trigger early puberty in girls

Worldwide, the number of girls experiencing early puberty has jumped sharply over the past decade. Puberty is the time in life when a person becomes sexually mature. When this process starts in girls under the age of 8, it’s called early puberty or precocious puberty. Early puberty can lead to social challenges and an increased risk of certain health problems later in life. These include heart disease, diabetes, and breast cancer.

Since the observed spike in early puberty in girls has been so sudden, scientists have wondered if compounds in the environment called endocrine-disrupting chemicals may be contributing. Endocrine-disrupting chemicals are natural or human-made chemicals that can mimic, block, or interfere with the body’s hormones.

The cascade of hormones that jump-starts puberty begins in a part of the brain within the hypothalamus that then activates cells in the anterior pituitary. Researchers still don’t entirely understand how the body triggers this cascade. But two receptors found on neurons in these regions, gonadotropin-releasing hormone receptor (GnRHR) and kisspeptin receptor (KISS1R), likely play a role.

Studies that have used blood or urine samples to look for chemicals that might activate these receptors could only reflect a brief snapshot of exposures in time. They also couldn’t look directly at effects on neurons.

To better understand how chemicals may affect GnRHR and KISS1R, a research team led by NIH scientists Drs. Menghang Xia and Natalie Shaw used engineered human cell lines that make GnRHR or KISS1R. They exposed these cells to about 10,000 compounds, including approved drugs and human-made chemicals found in the environment. Results were published on August 27, 2024, in Endocrinology.

The team identified numerous compounds that could activate the receptors. They then performed further experiments with a compound that activated KISS1R called musk ambrette. Musk ambrette is a fragrance molecule that may be found in products like soaps, detergents, and lotions.

In neurons that make KISS1R, exposure in the lab to musk ambrette turned on the gene for a molecule known to be produced when KISS1R is activated. Similar results were seen with five of the compounds that could potentially activate GnRHR.

To test the effects in a living organism, the team treated zebrafish embryos with musk ambrette during their development. Zebrafish and people develop in similar patterns, using the same processes and equivalent genes. Once hatched, the zebrafish larvae exposed to musk ambrette looked the same as those that weren’t exposed to chemicals. But the brain area responsible for releasing the hormones that trigger puberty was expanded in larvae exposed to musk ambrette.

“More research is needed to confirm our findings,” Shaw notes. “But the ability of these compounds to stimulate key receptors in the hypothalamus and pituitary raises the possibility that exposure may prematurely activate the reproductive axis in children.”

—by Sharon Reynolds