ENP95: Environmental Impact on Early Female Puberty

Summary

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Endocrine News Podcast Episode 95: Environmental Impact on Early Female Puberty

Release Date: December 4, 2024
Host: Aaron Lohr
Guest: Dr. Natalie Schall, Lasker Clinical Research Scholar, Principal Investigator at NIH’s National Institute of Environmental Health Sciences
Topic: Could environmental chemicals trigger early female puberty? Latest research and key findings.

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Episode Overview

This episode delves into the growing body of research on the effects of environmental compounds—specifically endocrine-disrupting chemicals—on the timing of puberty in girls. Host Aaron Lohr speaks with Dr. Natalie Schall about her team’s new study, which examines how certain environmental compounds may activate hormonal pathways in the brain, potentially leading to earlier onset of puberty.

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Key Discussion Points & Insights

1. The Alarming Trend of Earlier Female Puberty

[01:11] Dr. Schall:

• There is a documented trend toward earlier puberty in girls, seen in earlier breast development and menarche (first period).
• The change is relatively rapid, suggesting environmental rather than genetic causes.
• “It’s less clear if the same thing is happening in boys, but it’s happening at a relatively rapid pace, which suggests that it’s not related to genetic effects, but is caused by something in the environment.” (01:26)

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2. Environmental Chemicals as Endocrine Disruptors

[01:48] Dr. Schall:

• Many environmental compounds are endocrine disruptors; they can activate or inhibit parts of the endocrine system by binding to hormone receptors (estrogen, androgen, etc.).
• Such exposures can alter hormone-driven processes like puberty.

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3. Focus on Brain Pathways: Kisspeptin and GnRH Receptors

[02:20] Dr. Schall:

• Most research has targeted estrogen/androgen receptors; Dr. Schall’s study focused on kisspeptin and gonadotropin-releasing hormone (GnRH) receptors, central players in initiating puberty.
• “Puberty doesn’t start at the level of the breast. It starts in the brain and the hypothalamus.” (02:37)

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4. Methodology: High-Throughput Screening of Environmental Chemicals

[02:58] Dr. Schall:

• Collaboration with toxicologists at NIH’s NCATS (National Center for Advancing Translational Sciences).
• Used the TOX21 10K library—10,000 common environmental compounds.
• Screened compounds for activity on human kisspeptin and GnRH receptors using a cell line, then validated findings in human neurons and zebrafish.

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5. Noteworthy Findings and Surprising Results

[04:35] Dr. Schall:

• All findings were novel as these receptors haven’t been scrutinized for environmental activation before.
• The most striking discovery: musk ambrette, a fragrance compound in cosmetics, significantly activated the kisspeptin receptor.
• Cholinergic agonists also activated the GnRH receptor, but children’s exposure to these is less common.
• “[The] most interesting finding was this compound called musk ambrette, which is known to be in fragrances and cosmetic products. And we found that that activated this kisspeptin receptor.” (04:45)

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6. Implications for Everyday Exposure

[05:36] Dr. Schall:

• Musk ambrette may be widespread in consumer products, though actual exposure levels in children are currently unknown.
• “You can kind of buy whatever you want off Amazon and no one is really checking what’s in there... We really don’t know, and we don’t know in our children in the US are they being exposed to this compound in cosmetic products or not? And that’s something we need to study next.” (05:41)

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7. Dose and Hormonal Effects: It’s Not Always About Quantity

[06:34] Dr. Schall:

• Endocrine-disrupting chemicals can have effects at low doses, and sometimes it’s not the duration but the fluctuation of exposure that triggers hormonal changes.
• Example: In congenital adrenal hyperplasia, normalization (not excess) of hormone levels can sometimes trigger puberty onset.
• “It could be having an exposure and then the withdrawal of that exposure is actually what can trigger the system.” (06:46)

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8. Take-Home Message and Research Impact

[07:26] Dr. Schall:

• The study establishes a promising pipeline for screening and validating environmental effects on brain-puberty pathways.
• “It sets up a pipeline that other people could follow…high-throughput screen in a human cell line, validating in human hypothalamic neurons, and then further in an animal model.” (07:31)

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9. Future Research Directions

[07:50] Dr. Schall:

• Next steps include screening additional “puberty genes” and extending zebrafish studies to measure neuronal changes in response to environmental compounds.
• Use of fluorescent transgenic zebrafish to visualize effects on GnRH neuron populations.

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Notable Quotes

• Dr. Schall:
  • “It starts in the brain and the hypothalamus.” (02:37)
  • “All of it was surprising because I think no one’s really looked at these receptors and the potential for the environment to interact with them.” (04:37)
  • “We really don’t know [about children’s exposure], and that’s something we need to study next.” (05:52)
  • “Sometimes it’s not even a long exposure, it could be…withdrawal of that exposure is actually what can trigger the system.” (06:46)
  • “The way we approached this problem was really unique…sets up a pipeline that other people could follow.” (07:28)

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Key Timestamps

| Timestamp | Segment | Details | |-----------|---------------------------------------|----------------------------------------------| | 01:11 | Earlier puberty in girls | Trend description, suggested causes | | 01:48 | Endocrine-disrupting compounds | Mechanism of action | | 02:20 | Kisspeptin/GnRH focus | Rationale for choosing these targets | | 02:58 | Study methodology | TOX21 10K library, experimental design | | 04:35 | Major findings | Musk ambrette, cholinergic agonists | | 05:36 | Exposure assessment | Prevalence and regulation concerns | | 06:34 | Dose–response/withdrawal effects | Hormonal impact from low or transient doses | | 07:26 | Study significance | Unique pipeline, research implications | | 07:50 | Future research | Plans for further experimentation |

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Summary

This episode delivers an accessible yet rich exploration of how everyday environmental chemicals—especially those in fragrances and cosmetics—may directly impact the brain’s initiation of puberty in girls. Leveraging cutting-edge screening methods, Dr. Schall’s team has detected previously unrecognized risks and underscored the crucial need for new research on both exposure levels and health outcomes. Her paradigm-setting approach, moving beyond estrogen and androgen receptors to study brain-specific hormone pathways, opens new avenues for endocrine and public health research.

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Transcript

[A]

Hello, I'm Aaron Lohr, and this is the Endocrine News Podcast. There are plenty of studies showing that chemicals found in the environment can directly impact human health. Some new research finds that certain environmental compounds may trigger early female puberty. Joining me today to talk about that research is Dr. Natalie Schall, a Lasker clinical Research scholar and principal investigator of the Pediatric Neuroendocrinology Group in the Clinical Research Branch of the National Institute of Environmental Health Sciences. Dr. Schall is an author of a study recently published in Endocrinology entitled Identification of Environmental Compounds that May Trigger Early Female Puberty and By Activating Human Gonadotropin Releasing Hormone Receptors and kisspeptin receptors. So your study mentions that there is an alarming trend toward earlier puberty in girls. Can you tell us more about that trend and what may be influencing it?

[B]

Yeah. So there's been a trend of both earlier breast development in girls and a slightly smaller trend of earlier menarche or a girl's first period in girls. And I would say this has been happening over a number of decades and it's less clear if the same thing is happening in boys, but it's happening at a relatively rapid pace, which suggests that it's not related to genetic effects, but is caused by something in the environment.

[A]

Why might these environmental compounds have a significant impact on human health?

[B]

Well, a lot of the compounds, especially the ones that we study as endocrinologists, are known as endocrine disrupting compounds, which means that they can either activate or inhibit parts of the endocrine system. So we know, for example, there are a number of compounds that act at either at the estrogen receptor or androgen receptor.

[A]

And your study focuses on whether environmental compound could activate the kisspeptin and or the gonadotropin releasing hormone receptors specifically. Why did you want to study those two?

[B]

Well, I think there have been a lot of focus, like I said, on the estrogen and androgen receptors. And that makes sense that there could be compounds activating the estrogen receptor and that's what could be causing early breast development in girls. But puberty doesn't start at the level of the breast. It starts in the brain and the hypothalamus. And so I thought it'd be interesting to look specifically at some of the proteins and receptors in that pathway to see if any of the compounds in our environment could be acting directly in the brain.

[A]

Can you tell us about your study and what you and the team did?

[B]

I collaborated with a group of investigators at another branch of the nih, called ncats, which is national center for Advancing translational sciences. And these investigators are toxicologists who have access to something called the TOX2110K library, which consists of 10,000 compounds that are known to exist in the environment and that humans are exposed to. And so we were were able to do a screen of these 10,000 compounds and basically look at whether or not they were activating the GnRH receptor or kisspeptin receptor using a human cell line. And then we validated some of those studies using human hypothalamic neurons and zebrafish.

[A]

And the Tox 21 10K compound library. That sounds really interesting. So there's 10,000 compounds in there. Can you tell us a little bit more about how something might make the list?

[B]

I'm not sure exactly how the list is compiled, But I do know that there has to be a significant amount of evidence, again, that these are compounds in our environment, and then they'll look at what's known. So a lot of those compounds are already known to act at estrogen receptor, androgen receptor, or to be common things that humans are exposed to through cosmetic products, or they could be dietary supplements or pharmaceuticals, things like that.

[A]

And what did you find in your study? And I always love asking this, did anything in your results surprise you?

[B]

Well, all of it was surprising because I think no one's really looked at these receptors and the potential for the environment to interact with them. I think the most interesting finding was this compound called musk Ambret, which is known to be in fragrances and cosmetic products. And we found that that activated this kisspeptin receptor. We also found a class of compounds called cholinergic agonists, which activated the GnRH receptor. And that was interesting. But those compounds are things that children are less likely to encounter in their daily lives.

[A]

So I'd love to ask a little bit more about the musk ambrot and the cholinergic agonist. You know, you mentioned fragrances and that the cholinergic ones might not be as widespread in exposure, but it sounds like we talk about fragrances and things like that, that they might be more prevalent. Would it be true to say that mcmusk ambrit is not an entirely uncommon thing for people to end up having exposure to?

[B]

The way things are these days, you can kind of buy whatever you want off Amazon and no one is really checking what's in there. So I don't know. These regulations that exist only go so far, and I don't want to overstate what the exposure is? I think we really don't know, and we don't know in our children in the US Are they being exposed to this compound in cosmetic products or not? And that's something we need to study next.

[A]

You often hear about these endocrine disrupting chemicals and how exposures can have a myriad of different effects on the body. But one thing I've often heard is that the amount that you're exposed to might have an effect in a way that you, the one who doesn't study this, might not expect. You know, usually you'd think, well, if it's, if I get exposed a lot, then I'm going to have a lot of effect. But that might not always be the case with endocrine shipping chemicals. Can you talk a little bit about that, about how even maybe a little bit of a dose can have an effect?

[B]

I'm not sure if that's unique to the endocrine system, but we know even with endogenous hormone exposure that sometimes it's not even a long exposure, it could be having an exposure and then the withdrawal of that exposure is actually what can trigger the system. So we see that, for example, in a condition called congenital adrenal hyperplasia, where sometimes it's bringing their hormone levels under control, that can somehow actually trigger early puberty.

[A]

And when you think about your findings, and like you said, this is something that we haven't really seen much from before, specifically with the gonadotropin releasing hormone and cuspepin receptors. You know, what do you think is the take home message for folks? If you had to summarize, you know, the importance of this research, what would you tell folks?

[B]

I think the way we approach this problem was really unique and it's kind of sets up a pipeline that other people could follow. You know, doing these sort of high throughput screen in a human cell line, validating in human hypothalamic neurons, and then even further in an animal model.

[A]

And how do you think these findings might influence your future research?

[B]

We are planning to study additional puberty genes using a similar set of experiments and also conducting more experiments in zebrafish using the same transgenic line where basically you can measure the fluorescence of the GNRH neuronal population and look at how compounds might increase or decrease the area of those neurons.

[A]

Well, this has been a fascinating study to learn more about. I'm so thankful for you taking the time out of your day to share it with us. I look forward to hearing more in the future. Thank you so much. That's all for this episode. As always, thank you for listening to the Endocrine News Podcast. If you'd like to hear more of these, check us out on endocrine.org podcast or Apple, Google, or wherever you get your podcasts. And if you're enjoying these, please let us know by leaving a review on Apple. And if you'd like to get in touch with us, send us an [e-mail] thanks again. Endocrine News Podcasts are a free service of the Endocrine Society. To learn more or to become a member, visit the society's website at www.endocrine.org.