Page 311 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

278 SECTION | II Organ Toxicity

VetBooks.ir “Androgenic” and “Estrogenic” Effects “endocrine disrupting chemical,” “endocrine disruptor” or
“hormonally active agent” can be used interchangeably to
of Xenobiotics
discuss the actions of a given xenobiotic. However,
The terms “androgenic” and “estrogenic” and their anto-
nyms “antiandrogenic” and “antiestrogenic” have been whereas “endocrine disrupting chemical” and “endocrine
disruptor” generally have negative connotations and
used in a number of different contexts. Some authors
imply, by virtue of the inclusion of the term “disrupt,”
have used these terms to refer specifically to the agonistic
something “dangerous” and the likelihood of adverse or
and antagonistic receptor interactions of xenobiotics
toxic effects, the term “hormonally active agent” is more
(Hodgson et al., 2000). Because the precise mechanism of
benign and only indicates that a given xenobiotic has the
endocrine disruption of a given toxicant might not always
potential to affect a hormonal pathway in an animal
be known or might involve multiple mechanisms of
(Krimsky, 2001). As pointed out by Krimsky (2001),a
action, these terms have also been used in a more general
mechanism rather than a specific pathology is inferred by
sense, especially in livestock and wildlife species, to refer
“hormonally active,” and “hormonally active agent” is the
to phenotypic changes which were similar to or the oppo-
nomenclature preferred by the National Research Council
site of the effects which would be expected with exposure
(Knobil, 1999), especially when referring to xenobiotics
to endogenous androgens or estrogens (Guillette, 2006).
which interact with endogenous hormone receptors.
This type of general usage can be helpful in some
The circumstances and intended audience will often
instances but can also be confusing, given that xenoandro-
dictate the terms used to describe xenobiotics associated
gens and progestagens frequently have the opposite phe-
with or suspected of being having endocrine activity.
notypic effects as xenoestrogens. For instance, the effects
“Environmental hormone” and “environmental signal”
of estrogenic xenobiotics can be described as antiandro-
have also been used, along with “HAA,” “EDC” and
genic or anti-progestagenic in some instances, while the
endocrine disruptor, to describe xenobiotics capable of
effects of xenoandrogens and progestagens can be
interacting with endogenous hormone receptors
referred to as being antiestrogenic in nature. Further con-
(McLachlan, 2001; McLachlan et al., 2006). However,
fusion can be associated with exposures to mixtures of
the context in which these two terms have been routinely
chemicals having different phenotypic effects, as is often
used generally implies environmental contaminants with
the case in instances of environmental contamination, or
documented adverse endocrine effects on animals or
with exposures to xenobiotics having mixed antiestro-
humans. In some instances, the term “HAA” might be
genic and antiandrogenic effects (i.e., methoxychlor).
more “politically correct” (Krimsky, 2001) than “EDC,”
When the terms “androgenic,” “estrogenic” or their anto-
“endocrine disruptor,” “environmental hormone” or
nyms are used within this chapter, an attempt will be
“environmental signal” when discussing chemicals with a
made to clearly denote the intended specific or general
suspected hormonal activity that has not been clearly
meaning of the terms in the context in which they are
associated with adverse effects on animals in a research
used. The discretionary use of the terms “feminization”
and/or clinical setting.
and “masculinization,” as well as “defeminization” and
“demasculinization,” can also, in some instances, help to
clarify and/or describe the phenotypic effects of a chemi- Aryl Hydrocarbon Receptor-Mediated
cal suspected of endocrine disruption. Endocrine Disruption
Endocrine disruption mediated by the aryl hydrocarbon
Endocrine Disrupting Chemicals, Endocrine receptor (AhR) is a relatively complex, species- and
Disruptors and Hormonally Active Agents tissue-dependent phenomenon, involving several of the
previously described mechanisms of EDC action and
Any reproductive toxicant capable of endocrine disruption
interactions with many important, environmentally persis-
can be considered an “EDC” or an “endocrine disruptor.”
tent compounds. Some aspects of AhR-mediated endo-
Obviously, this includes a large number of xenobiotics
crine disruption are reminiscent of the ligand-induced
which are used in commercially available industrial, agri-
transcription associated with gonadal steroid receptor
cultural and pharmaceutical products, as well as naturally
function. However, the unique nature of the endogenous
occurring toxicants produced by plants and fungi. An
AhR and its interactions with primarily xenobiotic ago-
effort will be made later in this chapter to discuss some
nists warrants further discussion.
of the xenobiotics most often associated with endocrine
disrupting mechanisms of action.
Another term frequently used with respect to endo- Aryl Hydrocarbon Receptor Agonists
crine disruption, especially regarding xenobiotics which The major agonists for the AhR protein belong to the
interact with endogenous hormone receptors, is “hormon- class of environmental contaminants referred to collec-
ally active agent” or “HAA.” In most instances, tively as “halogenated” or “polyhalogenated aromatic