General and Comparative Endocrinology 257 (2018) 264–271

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General and Comparative Endocrinology

journal homepage: www.elsevier.com/locate/ygcen

Research paper

The clandestine organs of the endocrine system

Natàlia Garcia-Reyero
Environmental Laboratory, US Army Engineer Research & Development Center, Vicksburg, MS 39180, United States

a r t i c l e i n f o a b s t r a c t

Article history: This review analyzes what could be regarded as the ‘‘clandestine organs” of the endocrine system: the gut
Received 16 January 2017 microbiome, the immune system, and the stress system. The immune system is very closely related to the
Revised 13 August 2017 endocrine system, with many intertwined processes and signals. Many researchers now consider the
Accepted 15 August 2017
microbiome as an ‘organ’ that affects the organism at many different levels. While stress is certainly
Available online 16 August 2017
not an organ, it affects so many processes, including endocrine-related processes, that the stress response
system deserved a special section in this review. Understanding the connections, effects, and feedback
Keywords:
mechanisms between the different ‘‘clandestine organs” and the endocrine system will provide us with
Endocrine system
Neuroendocrine system
a better understanding of how an organism functions, as well as reinforce the idea that there are no inde-
Immune system pendent organs or systems, but a complex, interacting network of molecules, cells, tissues, signaling
Microbiome pathways, and mechanisms that constitute an individual.
Stress Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creative-
commons.org/licenses/by-nc-nd/4.0/).

1. Introduction activity is rapidly regulated to adapt to stress and maximize

The endocrine system consists of numerous glands throughout
the body that produce and secrete hormones in order to regulate
many physiological processes. The interconnections between the
endocrine system and the nervous system are considered the neu-
roendocrine system. In this review, both the endocrine and neu-
roendocrine systems are considered as a ‘large’ endocrine system.
It has been long accepted that there is a bidirectional communica-
tion between the endocrine and the immune system. Hormones
and neuropeptides have been shown to influence the immune sys-
tem in healthy and diseased individuals, and cells within the ner-
vous and endocrine system contain receptors for cytokines and
growth factors (reviewed in (Taub, 2008)). During times of stress,
communication between the immune, neuroendocrine, and endo-
crine system is vital for overcoming the stress and maintaining
homestasis. In fact, these interactions are so interwoven that some
researchers argue that the endocrine and immune system should
be considered one and the same (Schreck and Maule, 2001).
Stress response is a necessary mechanism to overcome chal-
lenges and restore homeostasis. Nevertheless, during non-
stressful conditions a low level of stress hormones is necessary
to maintain normal functions such as growth, immune response,
development or learning. The stress system is very tightly con-
nected with all the endocrine axes, including the reproductive,
growth, and thyroid axis, in order to ensure that the endocrine
E-mail address: natalia.g.vinas@erdc.dren.mil
chances of survival (Tsigos et al., 2016).
The idea that the microbiome, particularly the gut microbiome,
serves as a virtual endocrine organ has been suggested by several
researchers (Clarke et al., 2014; Evans et al., 2013). The concept
arises from the fact that the microbiome can produce and regulate
multiple compounds that reach and influence distal organs and
systems, such as the nervous, endocrine, and immune system.
The microbiome has also been described as a key regulator of
stress, further supporting the idea that it is not only a virtual endo-
crine system, but a major ‘virtual’ organ that could even be consid-
ered a system in the organism, with many connections, functions,
and influences at different levels (Evans et al., 2013; Rea et al.,
2016).
In this review we explore the interconnectivity between the
endocrine and neuroendocrine systems, the immune system, the
microbiome, and the stress response.
2. The stress system
Stress is part of everyday life and plays a key role on how organ-
isms perform necessary life functions, such as reproduction. The
term was originally proposed by Hans Selye and defined as ‘‘the
non-specific response of the body to any demand” (Selye, 1950,
1936). Other definitions have appeared since then. For instance,
stress was defined by Schreck as the ‘‘physiological cascade of
events that occurs when the organism is attempting to resist death
or reestablish homeostatic norms in the face of insult” (Moberg
and Mench, 2000; Schreck, 2010). The stress response involves a

http://dx.doi.org/10.1016/j.ygcen.2017.08.017
0016-6480/Published by Elsevier Inc.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 N. Garcia-Reyero / General and Comparative Endocrinology 257 (2018) 264–271 265

set of integrated cascades in the nervous, endocrine, and immune
system (Fink, 2016). It consists of three main stages: alarm, resis-
tance, and either compensation or exhaustion (death) (Schreck,
2010). The amplitude of stress responses depends not only on
the severity and duration of the stressor but also on other variables
such as genetic background of the organism, the environment,
prior experiences, epigenome, ontogenetic stage, and sex (Barton
et al., 1985; Lee et al., 2010; Momoda et al., 2007; Schreck and
Tort, 2016). Moreover, individuals within a population can differ
considerably in their response to stress (Ellis et al., 2012).
The endocrinology of stress, particularly in fish, has been
reviewed by others (Pankhurst, 2011; Schreck et al., 2016). Fig. 1
shows a summary of observed effects of stress on fish reproduction
and the potential mechanisms involved (adapted from (Pankhurst,
2016)). Stress generally has an inhibitory effect on reproductive
performance, although in certain conditions it can also have stim-
ulatory effects. The inhibitory effects include suppression of gona-
dal development, inhibition of ovulation and spawning, and
production of smaller eggs and larvae in fish. Other effects on the
endocrine system include suppression of hypothalamic, pituitary
and gonadal steroid hormones (Pankhurst, 2016).
Stress has also been linked to increased reproductive perfor-
mance, particularly through hormetic effects. For example, expo-
sure of the water flea Daphnia magna to low levels of several
compounds, including the energetic compound trinitrotoluene or
serotonin reuptake inhibitors, resulted in enhanced growth and
reproduction (Campos et al., 2012; Stanley et al., 2013). Another
example of improved reproduction was published by Haddi and
colleagues suggesting that males of the Neotropical brown stink
bug (Euschistus heros) hormetically increased their sexual fitness
after insecticidal stress in early adulthood (Haddi et al., 2016). Sim-
ilarly, Ayyanath and colleagues (Ayyanath et al., 2013) observed a
hormetic response in the form of increased reproduction in the
green peach aphid (Myzus persicae). Hormetic responses have been
observed across a wide range of stressors and organisms (Calabrese
and Baldwin, 2001), and are thought to be an overcompensation to
alteration in homeostasis. However, the concept is somehow con-
troversial and the reports are often inconsistent. For instance, a
hot event increased female lifespan and the length of the oviposi-
tion period but decreased the male net reproductive value in the
oriental fruit moth Grapholita molesta. Interestingly, both male
and female stress reduced egg hatch (Liang et al., 2014). Some of
these hormetic effects can also vary within generations. While
exposure of Daphnia magna to sublethal concentrations of chlor-
pyrifos negatively affected reproduction in the exposed generation,
it led to a significant increase in the number of offspring in the sec-
ond generation (Zalizniak and Nugegoda, 2006). Understanding the
threshold between hormetic and adverse effects, as well as the
potential accumulation of stress effects on the organism leading
to adverse outcomes even after apparently beneficial hormetic
effects, certainly warrants further investigation.
The delayed effect of stress on organisms and across multiple
generations is a fascinating subject getting increasing attention.
Some of the early observations on delayed stress effects led to
the ‘‘thrifty phenotype hypothesis”, which linked poor nutrition
in early life to permanent changes in glucose-insulin metabolism,
including insulin resistance, type 2 diabetes, and metabolic syn-
drome (de Oliveira et al., 2016; Hales and Barker, 2001; Vaag

Fig. 1. A summary of the hypothalamic-pituitary-gonadal axis in fish including a summary of stress effects on its different compartments. Upward arrows indicate
stimulatory effects and downward arrows indicate inhibitory effects. Text in compartments indicates suspected mechanisms of action. 11-KT: 11-ketotestosterone; 17,20bP:
17,20b-dihydroxy-4-pregnen-3-one; ACTH: adrenocorticotrophic hormone; CRF: corticotropin releasing factor; cyp19b1: aromatase b1; DA: dopamine; E2: estradiol; FSH:
follicle stimulating hormone; GnRH: gonadotropin releasing hormone; GR: glucocorticoid receptor; HSD: hydroxysteroid dehydrogenase; LH: luteinizing hormone; StAR:
steridogenic acute regulatory protein; T: testosterone; Vtg: vitellogenin; ZP: zona pellucida proteins. Adapted from Pankhurst (2016).
266 N. Garcia-Reyero / General and Comparative Endocrinology 257 (2018) 264–271
et al., 2012). Epigenetic mechanisms were believed to be involved
in those metabolic dysfunctions (Keating and El-Osta, 2015).
Another example of delayed stress effects can be found in Wang’s
studies on honey bees (Apis mellifera). Starvation stress during lar-
val development on the honey bee caused adult bees to become
more resilient to starvation. They were also characterized by
reduced ovary size, elevated glycogen stores, and juvenile hormone
levels, and decreased sugar sensitivity. Interestingly, adult bees
that experienced larval starvation were able to shift to other fuels
faster and maintain stable blood sugar levels during starvation, but
without changing metabolic rates or blood sugar levels under nor-
mal conditions (Wang et al., 2016a,b). In mammals, it is now sus-
pected that prenatal stress disrupts the normal surge of
testosterone in the developing male, while the associations differ
by species in females (reviewed in (Barrett and Swan, 2015)). In
rodents, prenatal stress feminizes male newborns by shortening
the distance between anus and genitalia. As adults, they also pre-
sent lower testosterone levels and fewer neurons expressing
androgen receptor in some areas of the brain (Pallares et al.,
2013; Fink, 2016). In humans, studies have shown that prenatal
stress does not affect the anogenital distance in males, but mas-
culinizes it (i.e. increases distance) in females, as well as increases
testosterone levels in adolescent females. Furthermore, prenatal
exposure to stressful life events has been associated with mas-
culinized reproductive tract development and more aggressive
play in adolescent females (Barrett and Swan, 2015; Fink, 2016).
Stress can also play a role in hierarchical dominance and even
sex change. For example, it is believed that psycho-social con-
straints (such as aggressive interactions), population density and
growth rate may play a role in sex change in fish from the protog-
ynous genus Thalosoma (Robertson, 1972; Ross, 1987). A case of dif-
ferential stress effects on hierarchical dominance can be found in
baboons. Observations in baboons showed that testosterone levels
responded differently after a stressful stimulus depending on their
rank in the hierarchy. Testosterone increased in dominant males
and remained elevated for about an hour, whereas it decreased in
subordinated males immediately after the initial increase, arguably
due to higher basal levels of glucocorticoids in subordinated males
compared to the dominant ones (Sapolsky, 1990).
Recently, genetic susceptibility is being explored as an extra
layer of complexity to understand the effects of stress (Fink,
2016). Caspi and colleagues (Caspi et al., 2002) suggested that a
polymorphism in the monoamine oxidase A gene influenced vul-
nerability to environmental stress in humans, which was linked
to aggressive behavior (Gallardo-Pujol et al., 2013). Post-
traumatic stress disorder (PTSD), a disorder that develops in some
people after a traumatic event, has also been linked to genetic sus-
ceptibility. Gillespie and coauthors described a sex-dependent
robust association between PTSD and a functional polymorphism
in the steroid 5a-reductase type 2 (SRD5A2) gene, previously
shown to lead to altered levels of steroid metabolism (Gillespie
et al., 2013). An earlier report of a polymorphism, a SNP in a puta-
tive estrogen response element in the gene coding for the PAC1
receptor, predicted PTSD diagnosis and symptoms only in females
(Ressler et al., 2011).
Taken together, all this information just begins to unravel the
complex network of physiological, genetic, epigenetic, and other
mechanisms governing stress responses and reveals exciting areas
of research that would further improve our understanding of
stress.
3. The immune system
There is a clear interaction between the (neuro) endocrine and
the immune system (Ashley and Demas, 2017), even in highly
divergent and evolutionary distant models such as molluscs, crus-
taceans, insects, and mammals (Kemenade et al., 2017; Malagoli
et al., 2015). Fig. 2 depicts the endocrine and neuroendocrine inter-
actions with the immune system and the microbiome. Those inter-
actions include the fact that the hypothalamic-pituitary-adrenal
(HPA, or interrenal in fish, HPI) axis is involved in suppressing the
inflammatory/immune response, as both innate and adaptive
immunity are modulated by glucocorticoids (Charmandari et al.,
2004; Chrousos, 2009). The main anti-inflammatory effects of glu-
cocorticoids involve changes in leukocyte function, decreased cyto-
kine production, and inhibition of pro-inflammatory signaling
pathways (Charmandari et al., 2004; Chrousos, 2000; Munck
et al., 1984; Tsigos et al., 2016). In fact, glucocorticoids also exert
potent anti-inflammatory effects by repressing proinflammatory
genes. They bind to the glucocorticoid receptor (GR) allowing it to
interact with transcription factors such as NF-kb that activates
many proinflammatory genes (Ghosh et al., 1998). The GR inhibits
the transcriptional activation activity of NF-jb by binding to the
promoter region of target genes (Webster and Cidlowski, 1999).
In a similar manner, estrogens can also exert anti-inflammatory
effects by binding to estrogen receptors (ER) that will consequently
repress expression of multiple NFjb-driven cytokines (An et al.,
1999; Heldring et al., 2007). There is also cross-talk between the
ER and the GR, which has been shown for proinflammatory genes
such as IL-6, IL-8, TNFa, and activator protein 1 (Ap1) (Cvoro
et al., 2017; Karmakar et al., 2013). Furthermore, GR can be
recruited to previously inaccessible chromatin regions after ER-
chromatin remodeling and co-activator interaction that will ulti-
mately modulate ER-regulated gene transcription (Bolt et al., 2013).
Endocrine hormones can also interact with the immune system.
Estrogens can bind to nuclear ERs, but they can also bind to the cell
surface G-protein coupled receptor GPER1/GPR30 (Thomas et al.,
2005) which is widely distributed in neural, ovarian, prostate, hep-
atic, and lymphoid tissues of mammals (Kemenade et al., 2017).
Both ERa and b are detected in the lymphoid organs, macrophages,
B and T lymphocytes, NK cells, and dendritic cells in mammals
(Mao et al., 2005). The immune-modulatory actions of estrogens
in mammals has been well documented (Kemenade et al., 2017).
Nuclear ERs have been detected in lymphoid tissues and leuko-
cytes of several fish species (Iwanowicz et al., 2014; Massart
et al., 2014; Pinto et al., 2012; Szwejser et al., 2017) and GPER1
has been reported on seabream granulocytes (Cabas et al., 2013).
For an in depth review of the immunomodulatory actions of the
HPG axis hormones see (Segner et al., 2017).
Just like the endocrine system can regulate the immune system,
the immune system also regulates the endocrine system. It has
been suggested that through this bidirectional communication
the organism should be able to redirect energy resources during
infection or stress away from endocrine functions in order to over-
come the stressor, infection, or disease. For instance, cytokines can
affect the HPG axis (Turnbull and Rivier, 1999). Interleukin 1 and
TNFa have been shown to inhibit the release of GnRH from the
hypothalamus and modulate FSH and LH release (Watanobe and
Hayakawa, 2003). Other immune system molecules such as thymic
peptides affect the HPG axis by stimulating GnRH secretion from
the hypothalamus and gonadotropin from the pituitary of female
rats (Bodey, 2007).
Stress certainly affects the immune system as well. Pathogens
can be considered as stress sources that affect the immune system
and can also affect reproduction (Schreck, 2010). Bonnet and col-
leagues proposed that pathogen-induced activation of the immune
system prior to ovulation could increase TNFa-mediated apoptosis
in trout ovary, advance ovulation, and result in egg quality
decrease after observing that TNFa decreased cell viability, stimu-
lated T production, and affected pathways involved in ovulatory
processes in trout (Bonnet et al., 2008).
 N. Garcia-Reyero / General and Comparative Endocrinology 257 (2018) 264–271 267

Fig. 2. Endocrine and neuroendocrine interaction with the immune system and the microbiome. Hormone and neuropeptide systems including sex hormones (estrogen,
testosterone, GnRH), stress hormones (corticosteroids ACTH), pituitary hormones (GH, prolactin), metabolic hormones (leptin, ghrelin), and opioids (such as endorphins) have
been shown to influence immune function. Immune cells express cell surface receptors for these hormones and peptides allowing responses to ligands. At the same time, cells
within the neuronal and endocrine systems can express receptors to immune-derived cytokines, and growth factors. The microbiome also interacts in a bidirectional manner
with the endocrine, neuroendocrine, and immune systems. Adapted from Taub (2008).

Similarly to pathogens, parasites can also be considered stres-
sors that might affect the endocrine system. Ramsay and col-
leagues showed that Pseudoloma neurophilia, a common disease
in zebrafish, can be associated with reduced weight and fecundity
(Ramsay et al., 2009a). Interestingly, this same parasite has also
been shown to affect behavior in zebrafish (Spagnoli et al., 2015).
Furthermore, stress has been shown to exacerbate parasite infec-
tion in zebrafish, further confirming the tight connections among
the nervous, endocrine, and immune systems and stress (Ramsay
et al., 2009a, b).
4. The microbiome
Lyte and Ernst first described the relationship between the
microbiome and endocrinology after observing that stress-
induced neuroendocrine hormones could influence bacterial
growth (Lyte and Ernst, 1992). Lyte later defined the term microbial
endocrinology as the study of the ability of microorganisms to both
produce and recognize neurochemicals that originate either within
the microorganisms themselves or within the host they inhabit.
The goal of microbial endocrinology is to understand the role of
microbiota in host behavior and the ability of the host to influence
the microbiota through neuroendocrine-based mechanisms (Lyte,
2004; Lyte and Cryan, 2014). The presence of neuroendocrine hor-
mones that have the same exact structure in bacteria and higher
organisms has been recognized for decades (Lyte, 2015). For
instance, the catecholamine family has been found not only in
mammals but also in bacteria, fish, plants, and insects (Ea et al.,
2000; Guerrero et al., 1990; Kulma and Szopa, 2007; Pitman, 1971).
Microbiota has been linked to behavior and development. It has
been shown to modulate behavioral and physiological abnormali-
ties associated with neurodevelopmental disorders, including aut-
ism (Hsiao et al., 2013). It is also known that gut bacterial
colonization has a role in the maturation of the immune and the
endocrine systems since birth (Clarke et al., 2014; Elahi et al.,
2013). Interestingly, the commensal bacteria can produce and
secrete hormones (Evans et al., 2013). The cross-talk between
microbiota and host hormones has been reviewed by (Neuman
et al., 2015).
There are many examples of bacteria affected by sex hormones.
Bacteroides melaningenicus can take up estradiol and progesterone
to enhance its growth, and changes in the expression of ERb have
been linked to changes in gut microbiota composition (Kornman
and Loesche, 1982; Menon et al., 2013). The interaction is bi-
directional, as several types of bacteria have been implicated in
steroid secretion or modification (Ridlon et al., 2013). Gut micro-
biome may also play a significant role in estrogen metabolism, as
suggested by data showing that antibiotic administration modified
estrogen metabolism in humans (Adlercreutz et al., 1984). Another
example showed that changes in gut microbiome were capable of
modulating zebrafish (Danio rerio) lipid processing by inducing
down-regulation of genes involved in cholesterol and triglycerides
metabolism, decreasing cholesterol and triglyceride content, and
268 N. Garcia-Reyero / General and Comparative Endocrinology 257 (2018) 264–271
increasing fatty acid levels, resulting in elevated larval growth
(Falcinelli et al., 2015). Furthermore, probiotic administration dur-
ing zebrafish development led to better reproductive performance
(Carnevali et al., 2013). There are other examples of microbiota
potentially affecting reproduction. Using gnotobiotic mosquitoes
(Aedes atropalpus and Aedes aegypti), Coon and colleagues showed
that gut bacteria species differentially affected normal develop-
ment and egg production (Coon et al., 2016). Similarly, another
study explored how microbiome influenced food choice behavior
and reproduction in the fruit fly Drosophila melanogaster, rescuing
the decreased reproduction induced by essential amino acid depra-
vation (Leitão-Gonçalves et al., 2017).
Recently, the microbiota has emerged as a key player in the con-
trol of the gut-brain axis in regulating stress-related responses
(reviewed in (Foster et al., 2017)). Nevertheless, the precise signal-
ing and feedback mechanisms remain to be completely elucidated.
A clear relationship between stress and microbiome was found by
Stothart and colleagues, who explored the linkage between stress
and oral microbiome on the red squirrel, and showed a correlation
between decreased bacterial diversity and higher stress levels
(Stothart et al., 2016). Gnotobiotic organisms have been used to
understand the interactions of the microbiome with the organisms,
including effects on behavior and stress. Fig. 3 depicts some of the
areas significantly impacted by the absence of normal microbiome
in rodents and zebrafish (Davis et al., 2016; Evans et al., 2013;
Fig. 3. schematic representation of areas significantly impacted by the absence of normal microbiome in rodent and zebrafish. Adapted from Smith et al. (2007).
Smith et al., 2007). The absence of microbiota dramatically altered
locomotor and anxiety-related behavior and affected acute stressor
response in zebrafish. Interestingly, treatment with the probiotic
Lactobacillus plantarum was enough to attenuate anxiety-related
behavior in gnotobiotic zebrafish (Davis et al., 2016). Other work
with germ-free organisms demonstrated a link between micro-
biota and anxiety-like behavior in rat and mice (Crumeyrolle-
Arias et al., 2014; Neufeld et al., 2011).
The microbiome can also affect the immune system. Kanther
and colleagues showed how the presence of microbiota in gnotobi-
otic zebrafish resulted in increased neutrophil number and altered
neutrophil localization and migratory behaviors, which led to
increased recruitment of neutrophils to injury (Kanther et al.,
2014). In another study, changes in zebrafish microbiome compo-
sition were associated with parasite stage of development and bur-
den, demonstrating that parasite infection can result in rapid and
temporally dynamic disruption of the zebrafish gut microbiome
(Gaulke et al., 2016). Microbial colonization in zebrafish has also
been shown to induce dynamic temporal and spatial patterns of
NF-jb activation in the zebrafish digestive tract (Kanther et al.,
2011). Gioacchini and colleagues showed that a probiotic mix acti-
vated the endocannabinoid system in zebrafish, highlighting its
potential to regulate immune cell function and providing clear evi-
dence of the involvement of microbiota changes on the zebrafish
immune system (Gioacchini et al., 2017).
 N. Garcia-Reyero / General and Comparative Endocrinology 257 (2018) 264–271
Exciting research is now showing how the immune system
develops alongside the gut microbiome, and studies exploring all
the different factors that might influence them are rapidly emerg-
ing. For example, researchers found that infants living with pets
had a higher diversity of microbes in their gut. As it has been also
shown that children growing with dogs have lower rates of
asthma, researchers believe that there is a link between gut micro-
biota development and allergic disease, probably due to exposure
to larger diversity of microbes such as those on dog fur (Azad
et al., 2013; Gupta, 2017).
While the study of the linkages between microbiome with the
endocrine, neuroendocrine and immune systems, and stress
response is a relatively new field of study, it is clear that the effects
are mutual and significant, opening plenty of opportunities for fur-
ther research leading to a better understanding of the very com-
plex system connections.
5. Conclusions
The systems biology paradigm that the whole is greater than
the sum of the parts, a holistic approach to deciphering the com-
plexity of biological systems that starts from understanding the
networks that form the whole of a living organism, summarizes
the concept described in this review that the endocrine, neuroen-
docrine, immune, and stress response system, and the microbiome
are just highly interconnected parts of the whole system and that
one cannot be completely understood without the other. The feed-
back mechanisms, signaling pathways and multidirectional rela-
tionships support the goal of an integrative approach to research
when trying to understand the different parts, or ‘‘clandestine
organs” of a system. Many issues remain worthy of further investi-
gation. The effects of genetic and epigenetic factors on stress, endo-
crine and immune responses across species still remain largely
unknown. The crosstalk between the endocrine system and its
clandestine organs is extremely complex, and I am convinced we
still need to understand many of their connections and signaling
networks, but techniques such as omics and some of the more
novel genomic engineering tools are certainly increasing our
knowledge of the system. And finally, still many research questions
remain when trying to understand the microbiome and its ties to
the other endocrine organs, opening plenty of exciting opportuni-
ties for targeted research.
Acknowledgments
This review was inspired by Prof Carl Schreck’s lecture entitled
‘‘Stress, haruspication and why the endocrine system is so similar
and also dissimilar amongst fishes”, at the 8th International Sym-
posium on Fish Endocrinology, where he talked about the similar-
ities of the immune and endocrine systems, and the effects of
stress. This work was supported by the US Army Environmental
Quality Research Program. Permission was granted by the Chief
of Engineers to publish this information.
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