Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 19 Adrenocortical Function
morning, leading to a diurnal rhythm of circulating cortisol
levels. The temporal coincidence between secretory bursts
and plasma ACTH concentrations indicates neuroendocrine
control.
In domestic animals and certainly in the dog, initially
there has been some controversy as to the occurrence of
circadian variation in cortisol concentrations. Later definite
evidence for episodic but not circadian fluctuations
in plasma cortisol concentrations in dogs was presented
( Kemppainen and Sartin, 1984a ). In the horse ( Dybdal
et al ., 1994 ) and the pig ( Benson et al ., 1986 ; Bottoms
et al ., 1972 ; Janssens et al ., 1995b ; Larsson et al ., 1979 ) as
well as in sheep ( Fulkerson and Tang, 1979 ), bulls ( Thun
et al ., 1981 ), pigeons ( Joseph and Meier, 1973 ; Westerhof
et al ., 1994 ), and chickens ( Lauber et al ., 1987 ), the occurrence
of circadian variations is generally acknowledged.
Also in the cat, there have been reports on the occurrence
of an (opposite) diurnal rhythm. However, in later reports
this was not confirmed ( Johnston and Mather, 1979 ; Leyva
et al ., 1984 ). As in the dog, the secretion is episodic without
evidence for a diurnal rhythm ( Peterson and Randolph,
1989 ). Apart from relatively short-term changes such as
episodic secretion and diurnal variation, plasma cortisol
concentration may change with age and during the estrus
cycle, during pregnancy, and around the time of parturition.
For example, basal cortisol concentrations in puppies
8 weeks of age or younger are lower than in mature dogs,
most probably because of reduced binding to plasma proteins
rather than to altered secretion patterns ( Randolph
et al ., 1995 ). In gilts a discrete cortisol peak occurs during
the early follicular phase of the sexual cycle, coinciding
with the decline in plasma progesterone levels (i.e.,
at 4 days before the plasma LH surge) ( Janssens et al .,
1995c ). Plasma cortisol concentrations of pregnant cows
decrease significantly during the fourth month of pregnancy.
Thereafter they remain fairly constant until the fifth
and sixth day before parturition, when a sharp rise is seen,
and also at around 24 h before parturition plasma corticoids
increase again ( Eissa and El-Belely, 1990 ).
A highly significant increase in basal plasma cortisol
concentrations occurs with aging in dogs ( Goy-Thollot et al .,
2006 ) with no differences in ACTH-stimulated plasma cortisol
concentrations. This confirms earlier studies ( Rothuizen
et al ., 1993 ) where the increased basal activity of the hypothalamo-pituitary-adrenal
axis is attributed to a decrease in
limbic type-I MR concentrations, whereby no differences
were found for the type II GR in canine brain structures.
The increase in pituitary type II GR with aging explains the
intact feedback in the aging dog ( Rothuizen et al ., 1993 ).
The ACTH-stimulated increase in plasma aldosterone concentrations
was found to be significantly reduced with aging
(Goy-Thollot et al ., 2006 ).
Independent of these physiological variations, it is
clear that stress may activate the pituitary-adrenocortical
system. Factors such as housing ( Carlstead et al ., 1993 ;
Cockram et al ., 1994 ; Koelkebeck and Cain, 1984 ), lactation
( Gwazdauskas et al ., 1986 ), exercise (Dybdal et al .,
1980 ; Foss et al ., 1971 ; Rossdale et al ., 1982 ; Sloet van
Oldruitenborgh-Oosterbaan et al ., 2006 ), surgery (Robertson
et al ., 1994 ), anaesthesia, heat ( Gould and Siegel, 1985 ),
emotional strain ( Bobek et al ., 1986 ; James et al ., 1970 ;
Kirkpatrick et al ., 1977 ), food deprivation ( Messer et al .,
1995 ), and anticipation of feeding ( Murayama et al ., 1986 )
all lead to increased corticosteroid secretion. In dogs, a
visit to a veterinary practice, orthopedic examination,
and hospitalization increased the urinary corticoid:creatinine
ratio, which is a measure for adrenocortical function
( Van Vonderen et al ., 1998 ). In the horse, during exercise
increased plasma renin activity results in a considerable rise
in aldosterone secretion ( Guthrie et al ., 1980, 1982 ). From
the lack of any increase in plasma corticosterone in homing
pigeons during flight, it was concluded that the animals were
not under serious stress ( Viswanathan et al ., 1987 ).
With chronic stress, such as during prolonged tethered
housing of pigs, an increased responsiveness of the adrenal
cortex to ACTH is induced, whereas the sensitivity of the
pituitary to stimulation with corticotrophin releasing hormone
(CRH) or vasopressin remains unaltered, and the challenge
(nose sling)-induced ACTH response is lower than in
loosely housed pigs. This indicates that during chronic stress,
mitigating mechanisms become operational, most probably
mediated by endogenous opioids ( Janssens et al ., 1995a ).
According to Selye’s theory of general adaptation, corticosteroids
are needed for the (metabolic and circulatory)
defense reaction. Administration of cortisol to improve
nonspecific resistance is indicated in established pituitary
or adrenal insufficiency. From an immunological point of
view, stress suppresses defense reactions. Stress-induced
glucocorticoid secretion prevents the overshooting of the
animal’s reactions to stress. The glucocorticoids modulate
the mediators of the immune system such as the different
lymphokines and mediators of the inflammatory reactions:
prostaglandins, leukotrienes, kinins, serotonin, and histamine
( Munck et al ., 1984 ).
It is now well established that the interaction of the
neuroendocrine system and the immune system is not a
one-way but a bidirectional communication. Tissue injury
or inflammation elicits production of immunoregulatory
cytokines (lymphokines and monokines) by macrophages
and monocytes. These cytokines also activate the pituitaryadrenal
axis and increase glucocorticoid concentrations,
whereas the production and action of these immune mediators
are inhibited by glucocorticoids. Thus, there is strong
evidence for the existence of a feedback circuit, in which
immunoregulatory cytokines act as afferent and ACTH and
glucocorticoids as efferent hormonal signals ( Besedovsky
et al ., 1986 ; Woloski et al ., 1985 ). The regulatory actions
of the cytokines are exerted at the level of the hypothalamus,
where CRH is the major mediator of the response
( Berkenbosch et al ., 1987 ), although cytokines also exert