Estrogen mimics at low doses change how brain cells manage dopamine.

[Guest guest]

Does this also explain some of the moulds that mimic estrogen have the

same effect?

" If the observations found in this study using

brain cells also occur in the brains of animals and people, the implications

are alarming. Specifically, chemicals common in the products, air, water and

food are potentially capable of profoundly altering brain chemistry at

extremely low levels; levels that most humans and many animals are exposed to

on a daily basis. "

Estrogen mimics at low doses change how brain cells manage dopamine.

Mar 03, 2009

http://www.environmentalhealthnews.org/ehs/newscience/low-level-EEs-alter-dopami\

ne-from-brain-cells/

Alyea, RA and CS . 2009.

Xenoestrogens alter dopamine transport and trafficking.

Environmental Health Perspectives doi:10.1289/ehp.0800026

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Synopsis by D. Laiosa and Hessler

For the first time, scientists find that extremely low levels of some types

of environmental estrogens disrupt specialized brain cells and their ability to

regulate brain chemistry. All of the EEs tested changed the way cells released

and reabsorbed dopamine, an important chemical messenger that governs movement

and pleasure.

J.P. Myers Warming a polycarbonate baby bottle will increase leaching

rates of bisphenol A.In some cases, the responses were stronger when natural

estrogens were mixed with one EE, as exposures most likely occur in people and

animals. These changes may explain how EEs contribute to nervous system

diseases, such as Parkinsons and schizophrenia, that are caused by abnormal

dopamine responses.

Xenoestrogens and other estrogen mimics are environmental contaminants that

act in ways similar to -- but not exactly like -- natural hormones such as

estrogen. Exposure to these chemicals, particularly at very low levels, can

cause biological outcomes that are not predicted by traditional experimental

procedures.

What did they do?

The authors tested whether different types of environmental estrogens (EEs)

affect dopamine signaling in rat brain cells. They tested the compounds by

themselves and then combined with estrogen hormones, as would occur in people

and animals. Levels tested were low, similar to what might be present in the

brains of people in the general population.

Cells derived from rat brains, called PC12 cells, were exposed to six estrogen

mimics, five of which are commonly found in the environment. The compounds

represented three major types of EEs: pharmaceuticals (diethylstilbestrol or

DES), plastic additives (BPA, nonylphenol) and pesticides (DDE, dieldrin and

endosulfan).

After exposing the cells, changes in dopamine regulation were measured.

Normally, brain cells release dopamine in response to an electrical or chemical

stimulus. After a period of time, cells reabsorb the dopamine and store it for

the next stimulus and release. The researchers measured both processes to

determine if the estrogen mimics affected release, uptake or both.

First, the authors measured how dopamine regulation changed through time. A

single, environmentally relevant dose (1nM or 1 part per billion) of the

estrogen mimics was added to cells. The amount of free dopamine outside of the

cells was measured every minute for up to 20 minutes.

Second, they chose the time point at which dopamine release was maximum for

each of the estrogen mimics and used that time point to ask if the maximum

dopamine release changed using a range of doses for each chemical.

Finally, in arguably the most important experiment of the paper, the authors

tested two estrogen mimics in combination with the natural estrogen hormone

17-beta-estradiol. This experiment replicates what would most likely happen in

people exposed to the chemicals.

Chemicals and normal hormones occur together in organisms. It is the

combination of the two (or more) that may have the most profound (and realistic)

impact on the chemical signals and ultimately, health.

What did they find?

In the first experiment, when compared to controls, treatment with 1 ppb DES,

DDE and dieldrin all caused a relatively slow but steady release of dopamine,

followed by either a leveling off or a reabsorption of dopamine. Nonylphenol

caused a slight release of dopamine, followed by a rapid and dramatic

reabsorption of the dopamine. Interestingly, bisphenol A caused a biphasic

response with two separate cycles of dopamine release and reabsorption.

In the second experiment, the authors measured changes in dopamine regulation

at a single time point across a range of concentrations. All of the estrogenic

mimics had more activity in the middle concentrations rather than at either the

lower or higher levels (displaying a non-monotonic dose response curve).

Non-monotonic dose response curves generally follow an inverted U shape, and are

commonly seen at extremely low concentrations of hormones or hormone mimics.

Finally, the authors tested how a dual exposure to either DDE or bisphenol A

and 17-beta-estradiol would affect dopamine regulation. The insecticide DDE

added with the estrogen increased dopamine release across a range of doses.

Combining estrogen and bisphenol-A affected dopamine regulation in a way not

predicted by the individual responses to either estrogen or bisphenol A.

Specifically, while bisphenol A caused a rapid reabsorption of dopamine at the

lowest dose tested, bisphenol A and estrogen together mediated dopamine release.

Moreover, at an intermediate dose where neither estrogen nor bisphenol A

affected dopamine release, the combination of the two caused significant

dopamine release.

What does it mean?

Each of the five estrogenic chemicals tested affected in different ways how rat

brain cells release and reabsorb dopamine. All acted at very low levels -- in

the parts per billion to parts per trillion range (less than a teaspoon mixed

into an Olympic sized swimming pool).

The responses were not linear across the doses tested; that is they did not

increase steadily as doses increased. The most profound effects were observed in

the middle dose ranges of the EEs tested. The higher levels did not affect

dopamine in the same way. Dose response experiments that show an inverted U

response are referred to as non-monotonic and are very common with xenoestrogen

responses.

The EEs acted through hormone receptors on the surface of the cell membrane,

instead of through receptors inside the nucleus. Surface receptors are much more

sensitive to low levels of exposure and their effects can take place much more

rapidly than receptors inside the nucleus. During the past 5 years, the surface

receptors have received considerable attention because of their unique traits

that better explain how some of the effects seen when testing EEs occur.

Finally, when two of the xenoestrogens were tested in combination with

estrogen, the effects on dopamine regulation were different than when each of

the chemicals was tested individually. The results of these experiments are most

likely what is happening in the real world where humans are exposed to mixtures

of contaminants. Moreover, these contaminants are interacting with and

interfering with normal biological regulatory factors, including, but not

limited to, hormones.

If the observations found in this study using brain cells also occur in the

brains of animals and people, the implications are alarming. Specifically,

chemicals common in the products, air, water and food are potentially capable of

profoundly altering brain chemistry at extremely low levels; levels that most

humans and many animals are exposed to on a daily basis.

Context Xenoestrogens, environmental estrogens, or simply, estrogen mimics are

natural and synthetic compounds found almost everywhere in the environment. They

can contaminate humans, animals, plants, soil, water and air.

The widely variable substances are present in plastics, PCBs, pesticides and

herbicides, pharmaceutical products, and personal care products. While the

amounts found in these products are often extremely small, the sheer volume of

items containing them makes exposure unavoidable.

People around the planet are exposed to estrogenic compounds on a daily basis.

The constant exposure to low levels may contribute to the potential to harm

human health.

Mounting evidence suggests that exposure to low levels of some EEs --

especially during development -- can cause a number of effects that can lead to

disease and reproductive problems later in life. Effects seen at lower doses may

not occur at higher doses or those at middle doses may not appear at the low or

high exposures tested. These variations -- common with hormones and

environmental disrupting compounds -- are known as nonmonotonic dose responses.

Prior laboratory studies show estrogen mimics can affect the brain by altering

important signaling chemicals that are regulated by estrogen hormones.

Dopamine is one of these specialized brain chemicals. Dopamine helps brain and

nerve cells communicate with one another. Its actions affect heart/circulation

(blood pressure), hormones (reward/pleasure) and nerve function (movement).

Dopamine is considered a neurotransmitter -- a messenger that carries signals

from one nerve cell to another -- and a hormone -- a molecule that sends

control messages to the hormonal system.

A number of diseases -- including Parkinsons, schizophrenia, attention deficit

disorder and addiction -- are attributed to problems with dopamine levels in

the brain.

Resources Dopamine. 3Dchem.com

Myers, J.P. and W. Hessler. 2007. Does the dose make the poison? Environmental

Health News.

Parkinson's Disease. National Parkinson Foundation.

Understanding Addiction: Dopamine. Addiction Science Research and Education

Center, University of Texas at Austin.

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