EDC Effects on Steroid Hormone Receptors in the Brain 217
hormones not only act on sex organs but also act upon the brain via steroid
hormone receptors that are not only expressed in the hypothalamus but are
also widely and heterogeneously expressed throughout the nervous system and
the rest of the human body. EDCs target the human brain in two basic ways:
by directly disturbing neuroendocrine balance that originates in the hypo
thalamus; and by binding the steroid hormone receptors and other signaling
pathways that occur much more widely throughout the brain and the body. In
humans, uncovering the effects of EDCs on the brain is difficult since the
analyses require postmortem tissues for which no studies are available.
Neuroendocrine neurons cannot be directly evaluated because hypothalamic
releasing hormones cannot be measured in peripheral blood samples, urine, or
other tissues. Therefore, human data are scarce and most of the findings are
based on behavioral consequences. However, it is not very difficult to surmise
the effects of EDCs on testosterone (ARs) and estrogen (ERs). As we discussed
earlier, the brain’s dense and widespread distribution of hormone receptors, its
high hormone sensitivity, and its ability to synthesize steroids through the
expression of steroidogenic enzymes, among other characteristics, make it
particularly vulnerable to hormonal‐like EDCs that disturb its fine‐tuned bal
ance. This is central to the idea that EDCs disturb the highly organized process
of brain development and contribute towards ASD, since there are critical
periods during which even minuscule fluctuations in hormone exposures can
affect a neurobiological outcome. This aspect of sensitive life periods is pivotal
in our understanding of the effects of EDCs on brain development.
EDC Effects on Steroid Hormone Receptors in the Brain
There is ample evidence that EDCs alter the degree of expression and distribu
tion of ARs and ERs in the developing central nervous system. This results in
interference in normal mRNA levels, protein expression, and neuroanatomical
changes to hormone receptors studied to date, as well as functional conse
quences of altered receptor action. In this book we cannot describe all the
adverse events from thousands of EDCs, but as an example we would like to
briefly mention two chemicals that have been shown to impart significant
alterations in a developing brain. Because these types of experiments cannot be
carried out on humans, we would like to present a small sample of research
carried out in zebrafish that were exposed to BPA for which there is the most
evidence for EDC activity on hormone receptors in the brain.
BPA is a compound used in the production of diverse consumer products,
ranging from baby bottles to thermal paper used for credit card receipts. Even
though adults can experience adverse health following continued exposure to
BPA, the fetal brain is especially vulnerable because of an immature xenobi
otic‐metabolizing system and the blood–brain barrier. A recent examination
