- Over the past decade, there has been a sharp global rise in girls experiencing early puberty, which may increase risks for health issues like heart disease, diabetes, and breast cancer.
- Scientists suspect that endocrine-disrupting chemicals in the environment might be contributing to this trend by interfering with hormones that regulate puberty, especially through receptors like GnRHR and KISS1R.
- Researchers exposed engineered cells and zebrafish embryos to these chemicals, finding that compounds like musk ambrette could activate key puberty-related receptors and potentially lead to premature activation of puberty in children.
Over the past decade, there has been a significant rise in the number of girls experiencing early puberty worldwide. Puberty is the phase of life when an individual becomes sexually mature, but when it begins in girls younger than 8 years old, it is referred to as precocious or early puberty. This condition can lead to social difficulties and heightens the risk of health issues later in life, such as heart disease, diabetes, and breast cancer.
Due to the sudden increase in early puberty cases among girls, scientists suspect that endocrine-disrupting chemicals in the environment might be a contributing factor. These chemicals, which can be either naturally occurring or man-made, have the potential to mimic, block, or interfere with the body’s hormonal system.
The process that initiates puberty is controlled by a cascade of hormones, starting in the hypothalamus—a part of the brain that activates cells in the anterior pituitary gland. Although the precise mechanisms triggering this process remain unclear, two receptors found on neurons in these regions, the gonadotropin-releasing hormone receptor (GnRHR) and the kisspeptin receptor (KISS1R), are believed to be involved.
Previous studies analyzing blood and urine samples to detect chemicals that may activate these receptors could only provide a limited snapshot of exposure and couldn’t directly assess their effects on neurons.
To gain further insight into how chemicals influence GnRHR and KISS1R, a team of researchers led by NIH scientists Drs. Menghang Xia and Natalie Shaw engineered human cell lines that produced these receptors. They then exposed the cells to around 10,000 compounds, including approved drugs and synthetic chemicals found in the environment. The results, published in Endocrinology on August 27, 2024, identified numerous compounds capable of activating these receptors.
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The team conducted additional experiments on one of the compounds that activated KISS1R—musk ambrette, a fragrance molecule found in products like soaps, detergents, and lotions. In lab experiments, exposure to musk ambrette triggered the production of a molecule typically produced when KISS1R is activated. Similar results were observed with five other compounds that potentially activated GnRHR.
To examine the effects in a living organism, the researchers exposed developing zebrafish embryos to musk ambrette. Since zebrafish and humans share similar developmental processes and genes, this model provided valuable insights. While the exposed larvae appeared the same as their unexposed counterparts, the region of the brain responsible for releasing puberty-triggering hormones was enlarged in the musk ambrette-exposed larvae.
Further research is needed to validate these findings, according to Shaw. “However, the ability of these compounds to stimulate key receptors in the hypothalamus and pituitary suggests that such exposures could potentially activate the reproductive axis prematurely in children,” she notes.
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