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

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Chapter | 19 Adrenocortical Function
TABLE 19-1 Relative Potencies of Corticosteroids
Corticosteroid Mineralocorticoid Activity Glucocorticoid Activity
Cortisol 1 1
Cortisone 0.7 0.7
Corticosterone 0.2 2
11-Deoxycorticosterone 0.0 20
Aldosterone 0.1 400
9 α -Fluorocortisone 10 400
Prednisone 4 0.7
Prednisolone 4 0.7
Dexamethasone 30 2
Triamcinolone 3 0
6 α -Methylprednisolone 5 0.5
kidney, but the intestine and spleen might also contribute
to a minor degree ( Balikian, 1971 ).
In domestic animals, the catabolism of androgens has
not been studied in any detail. For the dog, it is known
that little of the secreted androgens can be measured as
17-ketosteroids in urine ( Rijnberk et al ., 1968b ; Siegel,
1967 ). Probably most of the excretion occurs via the bile.
In the cat, glucocorticoid excretion is also largely biliary
( Rivas and Borrell, 1971 ; Taylor, 1971 ). Feline liver
function has several specific features, including a relatively
low glucuronyl-transferase activity. Hence, formation
of glucuronide conjugates is low, and the conjugates are
mainly sulphates, which are mostly excreted via the biliary
route. Despite this low urinary excretion of metabolites and
conjugates, it was shown that renal excretion of free cortisol
is sufficient for diagnostic purposes ( Goossens et al .,
1995 ) (see also Section IV.B).
Apart from the use of urinary excretion to examine the
glucocorticoid status, fecal glucocorticoid metabolite measures
are increasingly being used, especially for zoo and
wildlife animals. Interpretation of fecal glucocorticoids
may be confounded by a large variety of factors that should
be taken into account ( Millspaugh and Washburn, 2004 ).
F . Steroid Receptors and Actions
1 . Glucocorticoids
Of the naturally occurring glucocorticoids (cortisol, cortisone,
and corticosterone), cortisol is the most potent. Several
of the synthetic analogues of cortisol are more potent than
cortisol itself ( Table 19-1 ). Figure 19-5 illustrates the structural
features that determine glucocorticoid potency.
FIGURE 19-5 Structure-function relationships of corticosteroids. The
bold lines and letters indicate the structure common to all glucocorticoids.
Substituents that may enhance glucocorticoid activity are presented by
light lines and letters.
In their target organ cells, glucocorticoids act in the
same manner as other steroid hormones: diffusion through
the cell membrane; binding to the cytoplasmic, glucocorticoid
(GR), and mineralocorticoid (MR) receptors; translocation
of the hormone receptor complex to the nucleus;
and subsequent stimulation of the synthesis of specific
RNAs leading to synthesis of specific enzymes. The latter
include key enzymes in gluconeogenesis such as fructose-
1,6-disphosphatase, glucose-6-phosphatase, and pyruvate
carboxylase. In the dog, corticosteroid excess also results
in induction of an isoenzyme of alkaline phosphatase. This
corticosteroid-induced form of alkaline phosphatase has
not yet been found in other species. The marked stability
at 65 ° C allows easy quantitation in plasma as a diagnostic
screening tool for cases of suspected hyperadrenocorticism
( Teske et al ., 1986, 1989 ).
The traditional view is that the ligand activated GR
binds as a homodimer to response elements in promoter