Summary: New research reveals that girls exposed to certain endocrine-disrupting chemicals (EDCs) may experience early puberty, which is linked to various health risks. These chemicals, including musk ambrette found in personal care products, can stimulate key receptors in the brain that control puberty.
The study suggests that exposure to these substances could prematurely activate the reproductive system in children. Researchers recommend caution when using products containing unregulated chemicals to protect children’s health.
Key Facts:
- EDCs like musk ambrette may trigger early puberty in girls.
- Early puberty is linked to higher risks of obesity, diabetes, and breast cancer.
- Musk ambrette is still found in some personal care products despite safety concerns.
Source: The Endocrine Society
Girls exposed to certain endocrine-disrupting chemicals (EDCs) may be more likely to start puberty early, according to new research published in Endocrinology, the flagship basic science journal of the Endocrine Society. EDCs mimic, block or interfere with hormones in the body’s endocrine system.
There has been an alarming trend toward early puberty in girls, suggesting the influence of chemicals in our environment. Early puberty is associated with an increased risk of psychosocial problems, obesity, diabetes, cardiovascular disease, and breast cancer.
“We conducted a comprehensive screen of 10,000 environmental compounds with extensive follow-up studies using human brain cells that control the reproductive axis, and our team identified several substances that may contribute to early puberty in girls,” said study author Natalie Shaw, M.D., M.M.Sc., of the National Institutes of Health’s (NIH) National Institute of Environmental Health Sciences (NIEHS) in Durham, N.C.
Those substances include musk ambrette, which is a fragrance used in some detergents, perfumes, and personal care products, and a group of medications called cholinergic agonists.
“More research is needed to confirm our findings,” noted Shaw. “But the ability of these compounds to stimulate key receptors in the hypothalamus — the gonadotropin-releasing hormone receptor [GnRHR] and the kisspeptin receptor [KISS1R] — raises the possibility that exposure may prematurely activate the reproductive axis in children.”
According to the research team, musk ambrette is potentially concerning because it can be found in personal care products, and some rat studies have suggested it can cross the blood-brain barrier. Children are less likely to encounter cholinergic agonists in their daily lives.
Canadian and European regulations restrict musk ambrette use because of its potential toxicity, and the U.S. Food and Drug Administration removed the fragrance from its “generally recognized as safe” list. Yet it is still available on the market in some personal care products.
“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.
As part of the study, the research team screened a Tox21 10,000-compound library of licensed pharmaceuticals, environmental chemicals and dietary supplements against a human cell line overexpressing GnRHR or KISS1R.
They conducted follow-up analysis using human hypothalamic neurons and zebrafish, finding that musk ambrette increased the number of GnRH neurons and GnRH expression.
“Using human hypothalamic neurons and zebrafish provides an effective model for identifying environmental substances that stimulate the KISS1R and GnRHR,” said co-author Menghang Xia, Ph.D., from the National Center for Advancing Translational Sciences (NCATS) in Bethesda, Md., which is part of NIH.
“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.”
Other study authors include: Shu Yang, Li Zhang, Jameson Travers, Ruili Huang, Vukasin Jovanovic, Rithvik Veeramacheni, Srilatha Sakamuru, Carlos Tristan, Carleen Klumpp Thomas, and Anton Simeonov of NCATS; Kamal Khan and Erica Davis of Northwestern University in Chicago, Ill.; and Kristine Witt of the NIEHS Division of Translational Toxicology.
Funding: NIEHS and NCATS funded the study.
About this neurodevelopment and endocrinology research news
Author: Colleen Williams
Source: The Endocrine Society
Contact: Colleen Williams – The Endocrine Society
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Identification of Environmental Compounds That May Trigger Early Female Puberty by Activating Human GnRHR and KISS1R” by Natalie Shaw et al. Endocrinology
Abstract
Identification of Environmental Compounds That May Trigger Early Female Puberty by Activating Human GnRHR and KISS1R
There has been an alarming trend toward earlier puberty in girls, suggesting the influence of an environmental factor(s). As the reactivation of the reproductive axis during puberty is thought to be mediated by the hypothalamic neuropeptides kisspeptin and gonadotropin-releasing hormone (GnRH), we asked whether an environmental compound might activate the kisspeptin (KISS1R) or GnRH receptor (GnRHR).
We used GnRHR or KISS1R-expressing HEK293 cells to screen the Tox21 10K compound library, a compendium of pharmaceuticals and environmental compounds, for GnRHR and KISS1R activation.
Agonists were identified using Ca2+ flux and phosphorylated extracellularly regulated kinase (p-ERK) detection assays. Follow-up studies included measurement of genes known to be upregulated upon receptor activation using relevant murine or human cell lines and molecular docking simulation.
Musk ambrette was identified as a KISS1R agonist, and treatment with musk ambrette led to increased expression of Gnrh1 in murine and human hypothalamic cells and expansion of GnRH neuronal area in developing zebrafish larvae. Molecular docking demonstrated that musk ambrette interacts with the His309, Gln122, and Gln123 residues of the KISS1R.
A group of cholinergic agonists with structures similar to methacholine was identified as GnRHR agonists. When applied to murine gonadotrope cells, these agonists upregulated Fos, Jun, and/or Egr1. Molecular docking revealed a potential interaction between GnRHR and 5 agonists, with Asn305 constituting the most conservative GnRHR binding site.
In summary, using a Tox21 10K compound library screen combined with cellular, molecular, and structural biology techniques, we have identified novel environmental agents that may activate the human KISS1R or GnRHR.
