Exposure to cholinergic compounds, personal care products may lead to early puberty
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Key takeaways:
- Musk ambrette, found in some personal care products, increased stimulating activity in kisspeptin receptor cells.
- Five cholinergic compounds were identified as gonadotropin-releasing hormone receptor agonists.
Some types of endocrine-disrupting chemicals may act as kisspeptin or gonadotropin-releasing hormone receptor agonists and could induce early puberty for children, according to in vitro findings published in Endocrinology.
Researchers screened a large library of licensed pharmaceuticals and environmental compounds to identify agents that may activate the kisspeptin and gonadotropin-releasing receptors. Among the compounds identified were five cholinergic compounds that were considered gonadotropin-releasing hormone receptor agonists and musk ambrette, which activated the kisspeptin receptor. The link between musk ambrette and the kisspeptin receptor was especially worrisome, according to Natalie Shaw, MD, MMSc, the Lasker Clinical Research Scholar in the pediatric neuroendocrinology group of the National Institute of Environmental Health Sciences in Durham, North Carolina.
“Musk ambrette use has been restricted by several regulations because of its toxicity, yet it is still available on the market and still used in many inferior personal care products,” Shaw told Healio. “Children may therefore encounter musk ambrette and other nitro-musks through synthetic fragrances found in various household and personal care products.”
Shaw and colleagues screened the Tox2110K compound collection for possible kisspeptin receptor or gonadotropin-releasing hormone receptor agonists. After repeat calcium flux assays, 36 compounds were identified as gonadotropin-releasing hormone receptor agonists, two were considered to be kisspeptin receptor agonists and seven were found to be agonists for both hormone receptors.
Next, the researchers found 30 compounds that stimulated phosphorylated extracellularly regulated kinase activity in gonadotropin-releasing hormone receptor cells, including five cholinergic receptor agonists. Six compounds stimulated phosphorylated extracellularly regulated kinase in kisspeptin receptor cells. In further analysis, musk ambrette was the only compound to demonstrate increased stimulating activity in kisspeptin receptor cells compared with wild type cells.
Researchers confirmed the findings of musk ambrette stimulating the kisspeptin receptor during an in vivo study using zebrafish.
“Using human hypothalamic neurons and zebrafish provides an effective model for identifying environmental substances that stimulate the kisspeptin receptor and gonadotropin-releasing hormone receptor,” Menghang Xia, PhD, leader of system toxicology in the chemical genomics branch, division of preclinical innovation at the National Center for Advancing Translational Sciences in Bethesda, Maryland, said in a press release. “This study was a multidisciplinary team effort, and it showed that we can efficiently reduce the time and cost of assessing environmental chemicals for their potential effects on human health.”
Shaw said more research is needed to investigate whether exposure to musk ambrette in a real-world setting could lead to early puberty for children. She said future studies could compare compound levels of children experiencing early puberty with age-matched controls, and mouse studies could examine the effects of low-dose exposure to compounds on the reproductive system early in life.
In the meantime, Shaw advised providers to consider chemical exposure when assessing a child experiencing early puberty.
“This study suggests that, out of an abundance of caution, it is important for parents to only use personal care products for their children that are federally regulated,” Shaw said in a press release.
Reference:
- Girls may start puberty early due to chemical exposure. https://www.endocrine.org/news-and-advocacy/news-room/2024/girls-may-start-puberty-early-due-to-chemical-exposure. Published Sept. 10, 2024. Accessed Sept. 10, 2024.
For more information:
Natalie Shaw, MD, MMSc, can be reached at natalie.shaw@nih.gov.
Menghang Xia, PhD, can be reached at mxia@mail.nih.gov.