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The stress syndrome

B. M. FREEMAN
Houghton Poultry Research Station, Houghton, Huntingdon,
Cambs. PE17 2DA, England

Introduction
The zoological, let alone the biological, concept of stress continues to elude
satisfactory definition. Notwithstanding that the word is used widely in every day
speech, it is difficult to find a definition in the standard works of refercnce. Only
recently (1976) has the Concise Oxford Dictionary acknowledged that the word has a
biological dimension with an entry under stress disease. This is defined as a disease
suffered by managers etc. subjected to continual stresses: stresses is not
adequately defined. One fares little better with some scientific dictionaries, The
Dictionary of Biological Terms (8th edition, Oliver & Boyd) offers no definition;
Chambers Dictionary of Science & Technology confines itself to engineering.
Blakiston s Could Medical Dictionary (4th edition, McGraw-Hill) does manage an
entry-any stimulus or succession of stimuli of such magnitude as to tend to disrupt
the homeostasis of the organism; when incoordinate the stress may be considered an
injury, resulting in disease, disability or death. One further definition, in the form of
a mnemonic, deserves mention-Situations That Release Emergency Signals
necessary for Survival (Amoroso, 1967).
When viewed together it is clear that the common element of these three
definitions is that stress contains a negative element and that it should be avoided. But
two points of potential confusion can be detected in these definitions. The first is
whether the word stress is to be applied to adverse stimuli per se or to the
response(s) of the animal. The need for such a distinction has been recognised by Selye
(1951) who suggests stressors to describe the stimuli and stress to describe the
responses. The second point of confusion is less immediately obvious and is best
illustrated by Amorosos definition. He implies that stress is bad and yet the
emergency signals are clearly produced for good (i.e. survival). It would seem that
inherent in that definition is the seed of paradox. We shall return to this later. For the
moment it will suffice to ponder how the stress response can be recognised and
measured. What are, to use Amorosos words, the emergency signals?
Stress and Homeostasis
The Blackiston definition, given above, mentions homeostasis. This owes allegiance
to Claude Bernards famous dictum La fixite du milieu intkrieur est la condition
pour la vie libre, and inevitably drives the researcher towards studies on the
homeostatic control mechanisms.
The first major development was due to Cannon who elucidated the significance
of sympathin (i.e. adrenaline) in the so-called fight or flight syndrome
(Cannon, 1929) and unwittingly set the course of stress research for half a century or
more. It is clear from Cannons work that the two fundamental concepts of stress
were already acknowledged-that certain stimuli are noxious or life-threatening and
that life can only be preserved if positive countermeasures are taken. It is also
noteworthy that the significance of the adrenal gland had been recognised, though it is
due t o Seyle and his colleagues that both adrenal tissues, medulla and cortex, became
to be appreciated. The latters work culminated in the general adaptation syndrome

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(Selye, 1951) which proposed that there is a stereotyped set of physiological responses
which is set in train irrespective of the nature of the noxious stimulation. The adrenal
was apparently shown to play a central role in the adaptation syndrome; the
medullary catecholamines being active in the first or alarm phase, the cortical
glucocorticoids being secreted in the second or adaptive phase and, should these be
inadequate, a third phase (exhaustion) would be entered into with the homeostatic
mechanisms failing and death resulting.
In the half century since Selye made his entry into the field of stress (Selye, 1936) a
plethora of papers has been published confirming time and time again that a wide
range of stimuli-climatic, nutritional, physical, physiological, social
psychological-induce changes in adrenal activity. It is true that the proposed
precedent of the alarm phase over the adaptive phase does not always pertain, but
overall the ability of diverse stimuli to activate the adrenal has been amply
demonstrated. Two conclusions might be tentatively drawn from these findings-that
the adrenal is central to the stress response and that all stimuli that enhance adrenal
activity are stressors. However, neither can be sustained.
The Adrenal and Stressors
How is one to recognise stress? How does one recognise a stimulus as n o x i o ~ s ? ~
From the definitions already given one would assume some homeostatic disruption
or some disease or disability (or death) would need to be demonstrated. Given the
difficulty in establishing any of those criteria the solution seems to have been to rely
heavily on the Selye proposal of adrenal involvement. Similarly the same approach
has been evident in determining whether or not a stimulus is noxious and therefore
to be regarded as a stressor. But not all stimuli that affect the adrenal can be
classified as stressors nor can certain noxious stimuli that do not affect the adrenal
be assumed not to be stressors. It is ultimately a matter of human (i.e. the
observers) perception-at best a rather fallible sense. Thus high temperature is
considered a stressor because of the effects it has on man but no adrenal
involvement can be detected in the domestic fowl (Freeman and Manning, 1984;
Williamson et al., 1985). Similarly water deprivation is perceived as a particularly
pernicious stressor for man but not by the chicken (Freeman et al., 1983, 1984) nor,
indeed, does it seem to perceive the severe lesions of the gut caused by the parasite
Eimeria maxima as stressful (Davison et al., 1985a).
Other Endocrine Standpoints
At one time it might have seemed that the adrenal gland was not just dominating
research on stress but obscuring the minds of researchers to other homeostatic control
systems. But slowly, as more precise and sensitive techniques were developed, so other
endocrine glands were drawn into the orbit. Pancreatic glucagon was found to be
released under a variety of conditions in both mammals (Bloom eta/., 1973) and birds
(Freeman, 1980). Then the thyroid hormones were implicated (Kuhn and Nouwen,
1978). Others observed increased growth hormone and prolactin secretion (Harvey e f
al., 1978) or decreased concentrations of luteinizing hormone in the blood (Scanes et
al., 1976) under the influence of putative stressors. At the same time various
endocrinological interactions became understood: corticosterone affecting the
activity of phenylethanolamine N-methyltransferase and hence the conversion of
noradrenaline into adrenaline; corticosterone affecting the circulating concentrations
of the thyroid hormone (Davsion et al., 1985b).
Yet at the end, all these endocrinological events and inter-actions are no more
than homeostasis in action. Whether it is particularly relevant or useful to claim that

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they are therefore manifestations of the stress response seem less likely. Ultimately
any change in the concentration of any hormone is in danger of being explained in
terms of stress-a classic reductio ad absurdum. The significance of the acrophase of
the circadian rhythm of a hormone is an example.
Adaptation
Because of the power of Selyes hypothesis much has been done towards elucidating
the responses of the adrenal to putative stressors. Evidence abounds that if the
stimulus is prolonged, adrenal activity increases, reaches a peak and then gradually
falls to the initial value. This is generally assumed to indicate that the animal has
adapted to that stimulus. Insofar as it goes the assumption may be reasonable but it is
not reasonable to assume that an adrenal glucocorticoid is solely responsible for the
restoration of homeostasis. That variable was one of many involved. What makes it
disproportionately important is that it was measured.
Homeostatic adjustments are concerned with the preservation of the individual.
To assume that these forces for good can at the same time be bad seems paradoxical. It
must be admitted that secondary effects of biologically active substances may be just
that, but it seems that belief is to be unnecessarily stretched to assume that the
secondary effects may eventually become the primary ones.
Stressors-Their Current Status
The distinction between stress and stressors has already been noted though its value is
limited since stress still awaits an adequate definition. A wide range of stimuli have
been variously described as stressors, though often without sufficient evidence to
support that description. Tentative examples are grouped under various headings
(some might equally well appear under two or more of these headings):
Climatic (heat, cold)
Environmental (light, dark, transport)
Nutritional (excess salt)
Physiological (electric shock; anaesthesia)
Physical (immobilisation, crowding)
Social (changes in group structure)
Psychological (fear)
Within the limiting expectation that stressors are actually or potentially
damaging then it seems reasonable to describe all the examples given as stressors.
Nevertheless it has been noted that insufficient acknowledgement is made of
perceptive matters (see the section The Adrenal and Stressors). This component,
which is essentially psychological, is known to be particularly powerful in
humans-for example the anticipation of dental treatment can far outweigh the
treatment itself. Could it be that stressors, the stimuli that provoke damage, should
be identified as such only if they have a psychological component? If so then the
potency of any such stressor would decline as the target animal showed less developed
powers of memory, imagination and foresight.
The Demonstration of Stress
In view of the foregoing it seems inappropriate to label the various hormones, the
concentration of which have been found to be altered by the application of putative
stressors as stress hormones (see for instance, Bloom et al., 1973; Etches, 1976;
Freeman, 1980; Axelrod and Reisine, 1984). They are, by common consent, involved
in restoring homeostasis, not destroying it. Nevertheless it has to be admitted that the
glucocorticoids can affect lymphoid organs, but whether the effect is demonstrable

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under physiological, as distinct from pharmacological, conditions is less certain. Thus
bereavement has been shown to depress lymphocyte function without any
concomitant changes in the concentrations of cortisol, prolactin, growth hormone,
thyroxine or triiodothyronine (Bartrop et al., 1977).
Identification of new measures of stress has been neglected somewhat, most
probably because adrenal variables seemed satisfactory. As various new
endocrinological consequences of putative stressing have been recognised-glucagon,
triiodothyronine, thyroxine, prolactin growth hormone, luteinizing hormone-they
have been drawn into the tests for stress, only t o be abandoned later because they were
found generally to correlate poorly with any damaging effects observed. Selye was
well aware from the outset of two pathological consequences of stress-involution of
lymphoid organs and the development of ulcers. Either phenomenon would seem, for
the moment, t o be a better indicator of stress than any endocrinological change. A
third phenomenon has become recognised in recent years. It is the so-called stress
protein that is synthesised only under unusual (stressful) conditions.
In general the measurement of pathological sequelae seems more appropriate to
investigations into stress. Variables worth considering are: immunological function,
lymphoid organ size, lymphocyte numbers and natures of different subtypes,
development of ulcers and cardiovascular function. Reliance on measurement of the
concentrations of hormones is to take too facile a view of this fascinating, awkward
phenomenon.

Summary
Stress remains one of the most used, yet imprecisely quasi-scientific words in the English language. Its
meaning changes from situation to situation, from user to user. It is a word that is all things to all men.
There is, however, one common thread running through all its usages-stress acts to the detriment of the
wellbeing of the organism. Measurement of such detrimental consequences that can be reliably found
would therefore seem to be the appropriate way of examining the matter. Only when this has been done
should the mechanisms of pathological change be investigated.

RCsumC
LE SYNDROME DU STRESS
(B. M. Freeman)
Le stress reste lun des mots quasi-scientifiques de la langue anglaise les plus employes, quoiquimprkcis. Sa
signification change selon les situations et les auteurs. Cest un mot qui veut dire tout pour tous. I1 y a
cependant un fil conducteur commun qui court a travers tous ses usages-le stress agit au detriment du bien-
Ctre de lorganisme. La mesure fiable de ces Consequences defavorables qui peut &re trouvee semble donc
Ctre Iapproche approprike du sujet. Cest seulement appres que lon devrait rechercher les mecanismes du
changement pathologique.

Zusammenf assung
DAS STRERSYNDROM
(B. M. Freeman)
Der Begriff StreR ist einer der am hlufigsten aber auch am wenigsten prazise quasi-wissenschaftlichen
Worter der englischen Sprache. Seine Bedeutung wechselt von Fall zu Fall und von Person zu Person. Es ist
ein Wort, das fur viele alles mogliche bedeutet. Es gibt jedoch etwas gemeinsames, das bei jeglicher
Andwendung dieses Begriffs im Hintergrund steht-StreR wirkt schldlich auf das Wohlbefinden des
Organismus. Wenn es moglich ware, derartige schldliche Auswirkungen zuverlassig zu messen, ware dies
ein geeigneter Ansatz zur eingehenden Untersuchung dieses Sachverhaltes. Erst nachdem dies erfolgt ist,
sollte man mit der Untersuchung der Entstehung pathologischer Verlnderungen beginnen.

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Resumen
EL SiNDROME DE STRESS
(B. M. Freeman)
'Stress' queda una de las palabras del idiona ingles mas usadas, per0 imprecisamente y en un sentido demi-
cientifico. Su significado cambia de sitiacibn a situacion, de usador a usador. Es una palabra que es todas
cosas a toda la gente. Hay, sin embargo, un hilo comun que cone por todfas sus usadas-el 'stress' actua en
perjuicio del bienestar del organismo. La medida de tales consequencias perjuiciosas que se pueda
encontrar fiablemente pareceria entonces ser a1 metodo apropriado de examinar el sujeto. Solamente
cuando se ha hecho esto se pueden examinar 10s mechanismos de cambios phthologicos.

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