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Physician's Hair Institute

Physician's Hair Institute

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Published by Edith Ross
Part 2, Beyond Genetics, Evidence Suggests Endocrine Disrupting Chemicals (EDC's) Influence Our Hormonal Environment and Possibly AGA, Cyberchat, IsHRS Doctor Forum, Feb 2012
Part 2, Beyond Genetics, Evidence Suggests Endocrine Disrupting Chemicals (EDC's) Influence Our Hormonal Environment and Possibly AGA, Cyberchat, IsHRS Doctor Forum, Feb 2012

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Published by: Edith Ross on Jul 29, 2013
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Cyberchat: Part II Beyond Genetics
Evidence suggests Endocrine Disrupting
Chemicals (EDC’s) influence our hormonal environment and possibly AGA
 By : Sharon A. Keene, M.D.
In the last cyberchat column, a discussion began with Mike Beehner’s
presentationof monozygotic female twins who, despite their identical genotype, had remarkablydifferent degrees of hair loss. Subsequently, it was noted in a non-peer reviewedsurvey of monozygotic twins that differences in hair loss patterns were linked tosmoking, drinking (alcohol), stress and sun exposure. (1) However, no scientificexplanation was offered to support these findings. The report, however, introduceda conversation about epigenetic factors that may be influencing the genesresponsible for androgenetic alopecia (AGA) and causing variable rates and degreesof hair loss. In part II, the discussion of epigenetic influences continues with areview of the scientific evidence which reveals what for many will be unexpectedenvironmental exposures likely to influence our hormonal homeostasis andepigenetic cellular controls including hormonally mediated entities such as AGA. Inevaluating hair loss, it is important to recognize that although the recent focus onhair growth control and regulation has been via androgen metabolism andspecifically dihydrotestosterone (DHT), emerging molecular evidence points also tothe importance of estrogen responsive elements in the hair follicle which modifiesand interacts with androgens. A comprehensive review of this recent molecular
research has shown that hormones previously considered to be ‘female’, such as
prolactin and estrogen, have re-emerged as important modulators of hair growthand are, in fact, synthesized by the hair follicle. Add to this the growing evidencewhich indicates steroid receptors are able to cross communicate with each otherand we begin to understand the interdependent nature of steroid metabolism tohair growth in general,(2,3) and how regulation or interruption of these pathways islikely to influence AGA. Therefore, as we look to answer the question are thereenvironmental factors which can influence AGA? We must consider a complex, andas yet not fully described, interaction of androgens, estrogens, prolactin, as well asprogesterone, and the non-steroid, thyroid hormone, (4) too. All of these hormonesand their receptors and associated genes have been identified as influential in thehair growth cycle (2).To review, epigenetics refers to the non-DNA cellular controls that regulate geneexpression via activation/ silencing of genes, or up or down regulation of genetictranscription. The agouti mice studies referred to in Part 1 of this article, capturedthe attention of geneticists and nutritional scientists, by illustrating how dietarymanipulation with specific nutrients (methyl donors) altered genotype expressionresulting in dramatic phenotype variation in genetically identical mice. (5) Whenwe discuss dietary influence, we often neglect to consider that things we consumeinto our biologic medium need not be on a plate. They can be inhaled, swallowed orin some cases, touched and absorbed
so food is not the only issue that matters. It 
is the consumables we don’t know about that will be the discussion of this
column.Furthermore, before it is possible to identify potential environmental factors that may be influencing AGA in humans, it is necessary to understand the breadth of complexity in identifying and interpreting such molecular and epigenetic effects.
Epigenetic regulatory controls can be inherited, and passed transgenerationally
sosome gene expression seen in adulthood has been shown to be the result of experiences or influences from a great grandfather/grandmother. (6) Geneticvariants can determine the effects of an external exposure, for example, certainnutritional epigenetic influences vary according to particular geneticpolymorphisms
Vitamin D Receptor (VDR) polymorphisms can predispose tocolon cancer, and certain nutritional supplements can eliminate the increased
genetic risk which in contrast to the viewpoint ‘we can’t change our genetics’ .
While that is currently true, by manipulating gene activation or regulation we canchange the functionality of a gene. The study of the relationship betweennutritional supplements and genetic variation is called nutrigenomics. Some dietaryinfluences have been shown to vary based on pre or post natal exposure, as well asduration of exposure to the activating/deactivating mechanism which is often amethylation/demethylation or acetylation/deacetylation reaction. (7,8) Themethylation process has been mentioned previously as having a role in hair lossexpression relative to the Androgen Receptor (AR) gene. It is of interest to note that the most recent gene to be proposed as part of the polygenic entity of AGA is theHDAC 9 gene on Chromosome 7,(9) as this is a histone deacetylation genesuggesting a possible regulatory function in the activation of other genes. To furtherelucidate the complexity of epigenetic regulation, it must be noted that each cell inour body has an identical genome, and variable gene expression between cellsdifferentiates a liver cell, pancreatic islet cell, or a dermal papilla cell. The variablegene activation which differentiates cell types, may determine whether or how anepigenetic effect occurs for a particular cell. Epigenetic science has unveiled manyof the ways non-genomic controls create variable gene expression causing areassessment of assumptions about genetically predetermined disease inassociation with ethnic groups. This is important because while we cannot yet change the genome, epigenetic influences can be modified. Such modifyinginfluences include a group of environmental exposures referred to by researchers
as endocrine disrupting chemicals (EDC’s), which are ubiquitously used in the
industrialized world. While there may be wide variations in types and quantities of 
foods, EDC’s in industrialized countries offer a common exposure. These chemical
sact with estrogenic, androgenic, anti-estrogenic and anti-androgenic effects. It isinteresting to consider how our global economy and shared technologies may alsohave contributed to shared EDC exposure. Because of the ubiquitous nature of exposure to
EDC’s, as will be discussed, it is not possible to exclude them when
considering dietary influences for our patients, as they have become part of ourdiets either through direct exposure, or via the food chain. In the latter case, it hasbeen suggested we are what we eat-eats.In 2009 an Endocrine Society Scientific statement was published following a
comprehensive task force review of EDC’s which have been identified as able to
disrupt the normal endocrine axis in both animal and human studies. The result was a 50 page report outlining some of the identified chemicals or molecules, howthe exposure occurs, and the scientific evidence that profound and significant population exposures, even in small amounts, are influencing our biology andhormone homeo
stasis. The hormonal effects of these EDC’s are believed to cause
increases in diabetes, obesity, prostate and testicular pathology, polycystic ovarysyndrome as well as breast disease and cancer. While the Endocrine societystatement was not designed to specifically address hair loss in AGA, among thesubstances included in this review are those which have an effect on the hormonesinvolved in the hair growth paradigm. For those who would like a morecomprehensive review, the entire report is referenced and easy to download in aPDF format.(10) As defined by the U.S. Environmental Protection Agency (EPA) an
EDC is “an exogenous agent that interferes with synthesis, secretion, transport,
metabolism, binding action, or elimination of natural blood borne hormones that arepresent in the body and are responsible for homeostasis, reproduction, and
developmental process.” Researchers now have a broader understanding of theways EDC’s work, this includes their action on nuclear receptors such as androgen,
estrogen or thyroid receptors as well as enzymatic pathways for synthesis and
metabolism. EDC’s can be natural or synthetic. Exposure can occur via inhalation,
dietary consumption or dermal contact. Difficulties and limitations for interpretingEDC exposure effects include the fact that, as the EPA estimates ,we are beingexposed to hundreds of chemicals daily
making it virtually impossible to single out the effects of a single EDC in human models.The following is a list of some of the pertinent synthetic molecules mentioned inthe review article, their byproducts and ways they are used which contributes toour exposure, as well as the biologic effects noted in animals and/or humans whichdocument the hormonal effect of the chemical:
d biphenyls (PCB’s):
These are synthetic, lipophilic, halogenatedcompounds used in electrical equipment such as transformers, capacitors, heat transfer and hydraulic systems, also cutting oils and lubricants. PCBs have also beenused in products such as sealants, carbonless copy paper, paints, adhesives, plastics,flame retardants and to control dust on roads. Although their production in the
U.S. and Australia was banned in the late 1970’s, and heavy restrictions have been
imposed on their use in Europe since 1985, continued exposure occurs throughingestion of contaminated foods (fish, meat, dairy products, contaminated rice oil).
PCB’s can be transported long distances and have been identified far from locations
where they were manufactured or in use
having been reported in remote areas of 
the globe. Because PCB’s bioaccumulate with a half life of 1
-10 or more years, andaccumulate in adipose tissue, measurable levels are found in most of the USpopulation. (x) Epidemiological evidence across several different surveys includingthe U.S., Sweden, and Taiwan consistently showed an inverse relationship between
PCB’s and semen quality, with reduced sperm motility. Low levels were sufficient to
have an effect.
PCB’s have been shown to have estrogenic
and antiandrogenic activity.
PCB’s have been shown in animal models to reduce circulating levels of T4,
and can interact with the thyroid receptor. They have been observed to cause bothagonist and antagonist responses to the TR, with complex but deleterious effect. It is felt to be a neurotoxin in humans, with evidence of cerebellar sensitivity.

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