the external secretion ofthe pancreas in dogs

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Gut, 1961, 2, 338
The effect of corticotrophin and corticosteroids on
the external secretion of the pancreas in dogs
WILFRED SIRCUS'
Fronm the Department of Medicine, the University of Edinburgh, and the
Gastrointestinal Unit, the Western General Hospital, Edinburgh
In acute experiments in dogs cortisone and hydrocortisone increase the concentration
and output of bicarbonate in pancreatic secretion whereas prolonged administration of these
hormones leads to a diminished bicarbonate response. In both acute and chronic experiments,
however, cortisone and hydrocortisone produce an increased output of the enzymes amylase and
trypsin.
SYNOPSIS
There are several published reports of the effect of
corticotrophin and corticosteroids on gastric secretion in man and other species but only two, both
in man, concerning their effect upon pancreatic
secretion. Pfeffer and Hinton (1956) stimulated the
pancreas with intravenous secretin and insulin after
prior injection or infusion of hydrocortisone and
corticotrophin. Dreiling, Janowitz, and Rolbin
(1958) injected secretin, collected the duodenal
contents for a subsequent period of 80 minutes
and then, after injecting either corticotrophin,
hydrocortisone, or prednisolone, continued duodenal
aspiration for a further five hours. Amylase was
the only enzyme determined in each study. In
another paper Dreiling and Janowitz (1959) further
analysed the data from their original work. Both
groups of workers concluded that corticotrophin
and corticosteroids depressed the production of
bicarbonate and Dreiling et al. found a similar effect
on amylase. The present study was begun for two
reasons: first, to examine the effects of corticotrophin
and corticosteroids on pancreatic secretion under
more exact conditions in the dog, and secondly, to
gain more knowledge concerning the degree of tissue
specificity involved in such actions of corticosteroids
as the known one on gastric secretion.
The mode of action of corticotrophin and
corticosteroids on the parietal cells of the stomach,
or, indeed, on any glandular tissue, is uncertain.
There is evidence that steroids may affect the
d-amino acid oxidase enzyme involved in intracellular processes of oxidation and reduction
(Hayano and Dorfman, 1951; Umbreit, 1951). It is
'Part-time member of the external staff of the Medical Research
Council.
arguable that if the action on gastric secretion is
effected by influencing intracellular metabolism
then it should be as readily demonstrable in other
glandular structures of the alimentary tract with
exocrine function, including the pancreas.
METHOD
Two dogs were prepared for investigation of the effects
of long-term administration ofhormones by the formation
of an exteriorized loop of duodenum. At operation the
pancreatic accessory duct was found and divided between
ligatures. The duodenum was transected immediately
proximal to the main pancreatic duct and the proximal
portion anastomosed, end to side, to the fourth part of
the duodenum to restore alimentary continuity. The free
end distal to the transection was closed and brought out
of the abdominal cavity and permanently exteriorized
outside the recti muscles which were closed together in
the usual manner. A previously prepared skin flap was
then sewn around the exteriorized duodenal loop to
form a 'suitcase handle'. A silver cannula with a screw
cap was inserted into the anti-mesenteric border of the
loop immediately opposite the main pancreatic duct
(Fig. 1). Pancreatic secretion was subsequently collected
by placing a non-traumatic clamp across the skincovered loop immediately distal to the cannula. A small
closed chamber of about 2 cm. diameter was thus formed
around the main duct, and, in the erect position of the
dog, uncontaminated pancreatic juice flowed down the
cannula from which the cap had been unscrewed.
In three other dogs after likewise dividing the accessory
pancreatic duct a double or jacketed silver cannula
(Fig. 2) was inserted into the duodenum opposite to
the main duct opening. The duodenum was not otherwise
disturbed. Recovery of pancreatic juice was obtained by
advancing the inner tube until the conical flange at the
338
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The effect of corticotrophin and corticosteroids on the external secretion of the panc-reas in dogs
339
end impinged on the duodenal wall around the main
duct opening and thus isolated it.
In all experiments the pancreatic secretion was
collected under glycerol and in a container surrounded
by ice.
Amylase was determined by a modification of the
method of Lagerlof (1942), trypsin according to the
method of Gowenlock (1953) and expressed as Gowenlock
units, and lipase by the method described by Sammons,
Frazer, and Thompson (1956), using olive oil as the
substrate.
FIG. 1
PROCEDURES
EFFECT OF LONG-TERM ADMINISTRATION OF CORTISONE
FIG. 2
1. Skin-covered, exteriorized,
cannulated duodenal loop for collecting pancreatic secretion.
FIG.
2. A double cannula for direct
collection of secretion from the nmain
FIG.
pancreatic duct.
Two dogs were used and six control experiments made
on each to determine the normal response to the intravenous injection of secretin and pancreozymin.
Cortisone (cortisone acetate, Glaxo), either 25 or
50 mg., was given orally each day for 53 days to one dog
and for 120 days to the other, and the test procedure
repeated at intervals. Secretin and pancreozymin (Boots)
were given intravenously in a dose of 2 units/kg. body
weight. This dose was found to produce the maximum
response from the pancreas under normal conditions.
The design of the experiment was to collect fasting
pancreatic juice for 15 minutes, then secretin was
injected, and the response collected for 30 minutes. At
the end of that time the pancreozymin was injected and
the secretion collected for a further 30 minutes.
EFFECT OF LONG-TERM ADMINISTRATION OF CORTICO-
TROPHIN This study was carried out on one dog.
Control experiments were made to establish the
pancreatic secretory response to a standardized meal
and to secretin and pancreozymin.
Eight ounces of a proprietary food (Lassie) were fed
and pancreatic secretion continuously collected for
three hours. Tins of food from the same batch of
manufacture were used throughout.
The stimulating procedures were repeated at intervals
after beginning the daily intramuscular injection of
40 units of corticotrophin.
A capsule containing 1 g. of potassium chloride was
fed each day to the dogs in both groups.
EFFECT OF SINGLE INJECTIONS OF HYDROCORTISONE
Three
dogs were used to test the effect of single injections of
hydrocortisone on the pancreatic response to secretin
and pancreozymin.
Injection of hydrocortisone during continuous infusion
of hormones Secretin or pancreozymin was infused
intravenously using a motor-driven continuous infusion
apparatus (Palmer). When the volume output of the
pancreatic response had reached a plateau, 100 mg. of
hydrocortisone hemisuccinate sodium (Glaxo) was
injected intravenously.
Administration of hydrocortisone before injection of
secretin and pancreozymin One hundred milligrams of
hydrocortisone hemisuccinate sodium were injected intravenously either 15 or 30 or 60 minutes before the
intravenous injection of secretin and pancreozymin in
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340
Wilfred Sircus
30
L
A
40
1
4 5
2
9
7
FIG. 3. Dog F. The effect of cortisone on
the response to a standard intravenous
dose of secretin. The mean of the control
values is represented by the horizontal
line interrupting the cross-hatched first
block, and the extent of the cross-hatching
indicates the 1 in 40 confidence limits
(2 or 2S5 % probability value).
1
VOL.
IN E-i
10
2
4
5
6
8
7
9
10
12
UTPU20004
CONC. 100
AMYLASE
3
-
2744
MYLASE
UN6TS/m0
I20-
IN UNITS
A
400
30000-
OUTPUT
TRYPSIN
-
IN UNITS
C ONC.
L
OUTPUT
LIPASE
--
LIPASE
UNITNS*nl 2
-
lTU
n
H-
-IN UNITS
---[
2 3 4 5 6 7 8 9 10 11 12
~~~~BLOCK NOS
f-
'I 2 3 4 5 6 7 8 9 10 11 1I
(CONTfROLS)
0 19 26 34 48 57 62 70 79 86 93 126
DAYS ON CORTISONE
CUMULATIVE DOSE (mg.) 0 500 850 1250 1950 2400 2650 3050 3500 3850 4200 4725
the standard test detailed above and the results compared
with control experiments, omitting the hydrocortisone.
bicarbonate tended to fall whereas the concentration
and output of trypsin tended to rise. These effects
were
most evident during the second and third
RESULTS
months of administration. Significant increases in
In the text, results are only considered to be volume appeared episodically and in two tests the
significant when they differ from the control values concentration and output of amylase were raised.
The concentration and output of lipase were
by more than two standard deviations.
unaffected throughout (Fig. 3).
In dog E, only four experiments were made after
EFFECT OF PROLONGED ADMINISTRATION OF CORTISONE
ON RESPONSE TO SECRETIN In dog F there were beginning the administration of cortisone. The
considerable variations in the results over the whole output of bicarbonate was again found to be
period of cortisone administration but a striking reduced but no significant changes appeared in the
difference appeared between the effects on electro- concentration and output of the enzymes by the
lytes and enzymes. The concentration and output of fifty-third day, soon after which the dog died from
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The effect of corticotrophin and corticosteroids on the external secretion of the pancreas in dogs
341
available results show a reduction in concentration
and output of bicarbonate and a rise in concentration
and output of amylase and trypsin (Fig. 6). There
were no changes noted in the lipase response.
000
rnEqII.
ou HrI
IN
LL~~-~~ '
2
EFFECT OF PROLONGED ADMINISTRATION OF CORTICOTROPHIN IN RESPONSE TO A MEAT MEAL The
volume output was significantly reduced after the
administration of corticotrophin. Changes otherwise
appeared only in the bicarbonate response in which
the concentration was reduced in half the experiments
and the output in all. No significant changes were
noted in the concentrations and outputs of the three
enzymes (Fig. 7).
TRYPSIN 400
03.............
OUTPUT
0LOC
IN
~~~~~~~~RPIN
3i
4i Si1
IINITS/mL-2
4
..
H~~~~~BLCKOS
LASE
HCO3 60
F
3
2
OUTPUT
5
...-.
....
LIAS060
AL!LASE
UIN;/l
E
p
N UNITS
CONC.
M UAASE
30
a stndr intNUeTS 2dose o1 s
EFFECT OF PROLONGED ADMINISTRATION OF CORTICOTROPHIN ON RESPONSE TO SECRETIN AND PAN-
CREOZYMIN The results of only three experiments
were available and demonstrated a reduction in the
volume output, and the concentrations and outputs
of bicarbonate, trypsin, and amylase. The concentration and output of lipase was unaffected.
V00l---H
000r
600 7
mn
UNITS/mI
EFFECT OF HYDROCORTISONE ON RESPONSE TO A
5ale)
CONCor2r%probab2
TRYPSN
43
CUMULATIVE DOSE
(mg.)
600
250
0
750
)
ncroNCs4Dog
0omE.th7anl
The
cortisone
ofFg
FoG. 4.
on
dose of secretin.
effect
a standard
to
the control
intravenous
response
mean
of
is represented by the horizontal line
cross-hatched first block, and the extent
of the cross-hatching indicates the
dog 38 44ere
In confidence
perforation
from
of the duodenum
the
limits
1 in 40
COROSETISANRO ZYMI
DASON
b(2 or 2b5
% probability value).
a
the
The
values
interrupting the
necrosis
4
1200
caused by
pressure
(Fig. 8).
cannula (Fig. 4).
EFFECT OF PROLONGED ADMINISTRATION OF CORTISONE
ON
RESPONSE
again
PANCREOZYMIN
TO
significant
appeared
In
effects
dog F, there
upon
the
bi-
carbonate and trypsin components of the secretion
and also upon the volume output.
The volume was raised in the second and third
months of the tests,
as was
both concentration and
output of trypsin. Although the concentration of
bicarbonate
was
lowered in many tests the increase
in volume output caused
output
on
the tests
an
increase in bicarbonate
four occasions. Furthermore in most of
the output of
amylase
CONTINUOUS INFUSION OF SECRETIN Five experiments were made on three dogs.
In four an increase in the volume output appeared
within five minutes and persisted for up to one hour.
The mean increase was approximately 50% above
the maximum obtained before the injection of
hydrocortisone. The output of bicarbonate and
amylase was increased in four experiments and the
concentrations in three. In the two experiments in
which trypsin was estimated the concentration and
output were unaffected. Lipase was estimated in
only one experiment and the output rose substantially after the injection of hydrocortisone
was
significantly
EFFECT OF HYDROCORTISONE ON RESPONSE TO A
CONTINUOUS INFUSION OF PANCREOZYMIN Four
experiments were made on three dogs.
The results were more variable than those obtained
on the response to secretin.
The volume output and the concentrations and
outputs of bicarbonate, amylase, and trypsin were
all increased in two experiments, reduced in one,
and unchanged in the other.
An experiment is illustrated in which an increased
response followed the injection of hydrocortisone
(Fig. 9).
raised.
The output of
lipase
was
unaffected in all but
raised, as a result of
increases in volume output (Fig. 5).
In dog E, the only significant changes in the few
two
tests, in which it
was
EFFECT OF PRIOR INJECTION OF HYDROCORTISONE
UPON THE RESPONSE TO SINGLE INJECTIONS OF THE
PANCREATIC HORMONES Hydrocortisone, 100 mg.,
was injected intravenously 10 to 15 minutes before
Downloaded from http://gut.bmj.com/ on June 18, 2017 - Published by group.bmj.com
342
Wilfred Sir.cus
FIG. 5. Dog F. The effect of cortisone on
30_
the response to a standard intravenous
dose of pancreozymin. The mean of the
control values is represented by the
VOL.
_
20
IN
..........._
2 3 4 5 6
_L_X
7 8 9
T 4T-OUTPUT
HCO3 2
1IN mEq.
CONC. 200 _
HCO3 100 9.--IN mEq./I1.
_ _
I
m0lloH-L!jiliEJjJ1J1-Lml.
L_
horizontal line
i
interrupting the cross-
hatched first block, and the extent of the
cross-hatching indicates the 1 in 40 confidence limits (2 or 2 5% probability
tO 11
value).
-
n
1000
OUTPUT
E
--_ bp..
LLii
-
600 AMYLASE
IN
FEl
-200
UNITS
OUTPUT
400_
LIPASE
CONC.
LIPASE
IN
UNITS/ml.
-
IN UNITS
2
3
4:
S 16 .8 Lll.1
3
4
5
6
7
8
9
10
BLOCK NOS.
2
3
4
5
6
7
8
9
10
11
(CONTFLS)
DAYS ON CORTISONE
CUMULATIVE DOSE(mg.)
0
19
26
0
500
850
34 48 62 70 79 86 93 126
1250 1950 2650 3050 3500 3850 4200 4728
injecting secretin or pancreozymin. Two experiments
were made with each hormone in two dogs, and in
all four there appeared a substantial increase in the
concentration and output of bicarbonate and
amylase (Figs. 10 and 11). The other enzymes were
not determined in this group of experiments.
The effect of injecting hydrocortisone 30 minutes
before secretin and 60 minutes before pancreozymin
was tried. Seven control experiments determined the
standard response. Two experiments were made with
each hormone after the administration of the steroid.
In none of the four experiments was any effect
noted upon volume, concentration, or output of
bicarbonate, amylase, lipase, and trypsin.
In most of the experiments in which an increased
volume response was obtained there also appeared an
increase in the concentrations of the bicarbonate
and enzymes. Thus the augmentation of output
after hydrocortisone is unlikely to be the result of
an increased 'washing-out' effect of enzymes from
the duct system.
DISCUSSION
The results clearly indicate that the pancreatic
response, both of electrolytes and enzymes, to
stimulation by meals, secretin, and pancreozymin
can be influenced by corticotrophin and steroids.
The depression of pancreatic secretion after
corticotrophin was noted in a single dog but the
result confirms the observations of Pfeffer and
Hinton and Dreiling et al. previously quoted. In
Downloaded from http://gut.bmj.com/ on June 18, 2017 - Published by group.bmj.com
30
VOL.
-
_
20
.
- .
-
IN
N10 _
mi.~l
2
23 4
IN
401HIlNliI
1200r
1 2 3 4 S
CONC.
OUTPUT
CONC.
HCO3
HCO3
HCO3
IN
IN
mEq.1 1.
mE-qJI.
IN
UNITS
1000-
CONC.
r
-
TRYPSIN 600'IN
(NITS/ml. 200 I
CONC.
Ll PASE
IN
40-
UNITS/mIl.
OUTPUT
-1----i-
40
2
...--.-(4672)
IN 2000
1000-
n
UNITS/mi '-
---
---
AMYLASE
UNITS
-
-
(81950)--
80000
IOOOOT
OUTPUT
F
60000k
TRYPSIN
TRYPSIN 6000IN
UNITS 2000- _
~--
-----
-
IN
..--TS
200
-...........
4000
OUTPUT
80 .-
-60 -3000OUTPUT
AMYLASE
-
4
2mEq. L
--IN
40
CONC.
1000AMYLASE 600
343
-.1
IN
_
40000L
20000-
UN ITS
~ ----
CONC. 50L
.
A
LIPASE
OUTPUT
200-- 2000
0 -----IN
W
IL
;.02
L
L
1
20
~~~~~~~~1LIPASE30LPE
77 UNITS
IPS
IN
3 4
2
UNITS/mI. 10
IN UNITS
2
3
4
2 3 4 5
r
2
3
45
BLOCK NOS.
1
2
3
4
38
600
44
53
750
1200
2
(CONTROLS)
0
DAYS ON CORTISONE
CUMULATIVE DOSE (mg.) 0
FIG. 6
DAYS ON ACTH
CUMULATIVE DOSE (UNITS)
BLOCK NOS.
3 4
5
0 12 20 40 48
0 480 800 1600 1920
FIG. 7
~K"OU INfUSION Of SECRETIN 0-5u/MIN
iO mg. i.v.
+ ~~~~H.C.
5 .
4
VOLUME
3
1100
HcoI 04F5[
0
_80 HCO0
OUTPUT 03
mE)0.2
(UNITS)
C0I4C
-
200
AMYLASE 160F
OUTPUT 120
80PU
-2
--
=-
-
40
so-
40
--
50-1oAMLS
A-YLASE
30
-
10
40
2
4200
TRYPSIN 3600
3000-
1200
1000 TRYPSIN
800
1600 CONC.
--8-
OUTPUT 24001-
18001-
1400 (UNITS/mIl
200
(L ITS) 1200
600
LIPASE
OI
25
-
81
LIPASE
-~~~~~~~~~~~~2.0
CUTPUT
6j(UNITS)
4-N215 30 45
FIG. 8 MI-NS.
CONOC
IUNITS/mI~
-
60
75
90
105 120
IS-----I CONC.
05 (UNITSiml .)
TS"O
135
150 165
FIG. 6. Dog E. The effect of cortisone on the response to
a standard intravenous dose of pancreozymin. The mean
of the control values is represented by the horizontal line
interrupting the cross-hatched first block, and the extent of
the cross-hatching indicates the 1 in 40 confidence limits
(2 or 2.5 % probability value).
FIG. 7. The effect of corticotrophin on the response to a
standard meal. The mean of the control values is represented
by the horizontal line interrupting the cross-hatched first
block, and the extent of the cross-hatching indicates the
1 in 40 confidence limits (2 or 2-5 % probability value).
FIG. 8. The effect of hydrocortisone (H.C.) on the
pancreatic response to a continuous infusion of secretin.
A typical experiment (9 March 1959).
-
-
.--
=_ output
- -=
concentration
Downloaded from http://gut.bmj.com/ on June 18, 2017 - Published by group.bmj.com
Wilfred Sir.cus
344
CONTINUOUS INFUSION OF PANCREO
05
H S2
SI
tIN
u/MIN.
4-
4I
Sl
H S2
IlA)) n
VOLUME
(Ml.)
5
3
O0
HCO3
0.13-
07HCO3
OUTPUT 06r-
+
OUTPUT
0.4
(m E q)
0.30..
-~~~~~~~~~~100
4
O.1
0C-C
(mEq.1I.)
120
so-~
~~
~
r
~
~
-0
200h
160
(UNITS)
80
40
+
1200
44-St
-8
60
-
HCO3
O4020 (mEq./=.)
CONC.
H Sz
r20 AMYLASE
10
|
MINS.
AMYLASE
(UNITS/mC)
-5
(UNITS)
OUTPUT
OUTPUT
~~~~~2
-
40
-----
280 F
AMYLASE 240
_
OUTPUT
TRYPSIN
(mEqo
HCO3
80
-
AMYLASE
----
-
0.
060.5
r----~
3o
60
5
90
120
CONC.
(UNITSIMt.)
150
10
FIG.
1200
600.
(UNITS)
50(
MINS. 15
30
45
60
75
90
105 120
(UNtS/mi.)
155
FIG. 9
The effect of hydrocortisone on the pancreatic
continuous infusion of pancreozymin (18
March 1959).
FiG. 9.
response to a
=
-
- - - - - - -
-=
output
2
concentration
FIG. 10. The effect of hydrocortisone injected 10 minutes
beforehand on the pancreatic response to a single injection
of secretin (29 April 1960).
Si. 60 units secretin in 1 ml. distilled water intravenously.
S2. 60 units secretin in 1 ml. distilled water intravenously.
H. 100 mg. hydrocortisone hemisuccinate sodium in 1 ml.
distilled water intravenously.
=
- - - - - - - - -=
VOLUME
(ml.)
Pi
---
P2
--
'---~~~~~~
`30
20
.
f
1
---
HCO3
CONC.
(mE%/I.)
concentration
200
1 1. The effect of hydrocortisone injected 15 minutes
beforehand on the pancreatic response to a single injection AMYLASE 160O
ofpancreozymin (4 May 1960).
P1. 100 units pancreozymin in 3
ml.
distilled water
intravenouslv.
P2. 100 units pancreozymin in 3 ml. distilled water
intravenously.
H. 100 mg. hydrocortisone hemisuccinate sodium in
3 mL. distilled water intravenously.
=
-
output
FIG.
- - - - - - - -
H
HCO3 0-2
OUTPUT
(mEq.)
1
1
OUTPUT 120-
(UNITS)
80-
40
CONC.
-2030AMYLASE
40
---
2
MINS 15
output
--= concentration
;
FIG.
11
30 45
1
- 1
60
75
0
90 105
0
(UNITS/mI.)
Downloaded from http://gut.bmj.com/ on June 18, 2017 - Published by group.bmj.com
The effect of corticotrophin and corticosteroids on the external secretion of the pancreas in dogs
the Edinburgh Gastrointestinal Unit we have noted
that profound depression of gastric secretion
may accompany the prolonged administration of
corticotrophin to patients (Crean, 1961) although
the effect is unpredictable in the individual subject.
Hirschowitz (1956) reported similar depression of
gastric secretion with dramatic clinical sequelae in
volunteer human subjects infused with corticotrophin. It is only possible to speculate on the
significance and mechanism of the depressed
secretory response of exocrine glands after the
administration of corticotrophin, as the available
preparations are crude with variable potency and,
possibly, of variable chemical constituency. On the
one hand, corticotrophin has been shown capable
of producing acinar ectasia and fat necrosis (Carone
and Liebow, 1957) and, on the other, hypophysectomy may result in atrophy of the pancreas with
repair on the subsequent administration of corticotrophin (Patterson, Dingman, Shwachman, and
Thorn, 1954; Kinash and Haist, 1954).
There were striking differences in the effect of
cortisone and hydrocortisone upon bicarbonate and
the enzymes. In acute experiments the concentration
and output of bicarbonate were usually raised
whereas prolonged administration of hormones
appeared to depress the bicarbonate response, as
noted by previous workers. But in both acute and
chronic experiments the effect of cortisone and
hydrocortisone was essentially to increase the
concentrations and outputs of the enzymes although
the relative resistance of the secretion of lipase to
these influences is notable. The difference in the
bicarbonate responses in acute and chronic experiments is as yet inexplicable, especially as structural
hyperplasia in the pancreas of experimental animals
given cortisone has been found to affect both the
epithelium of the ducts (Bencosme and Lazarus,
1956) and acinar cells (Sesso and Oliverio, 1959).
At whatever site the electrolytes and enzymes of
pancreatic secretion are respectively produced,
both may be affected.
It has been postulated (Green, 1941) that
hormones act by participating in, or specifically
affecting, enzyme systems. It may be that the enzyme
systems involved in the intracellular production of
exocrine secretions are similar in the different glands
of the alimentary tract. Thus studies with thiadiazole
compounds have suggested that carbonic anhydrase
plays a part in both gastric and pancreatic secretion
(Davies, 1951; Birnbaum and Hollander, 1953).
The immediate effect of steroids upon the intracellular enzymes could result in augmenting the
secretory output, while the cumulative effects of
prolonged administration may be exerted through
the structural hyperplasia previously reported. It
5
345
was found that the action of a single injection
appeared within five minutes and was never
prolonged beyond one hour. Furthermore, the effect
was so transient that if it was given 30 minutes or
more before the injection of hormones which
stimulate the pancreas no effect could be discerned.
I have also noted similar characteristics in the effect
of steroids on gastric secretion in dogs.
I wish to thank Mr. W. Forshall, of the Biochemistry
Laboratory of the Edinburgh Northern Hospitals Group,
for most of the biochemical estimations, and also the
Director, Dr. L. Tompsett; Dr. E. Morton, of Boots
Pure Drug Co. Ltd., for supplying part of the secretin
and pancreozymin; Mr. D. Wright, of the Department
of Medicine, for the diagrams; and Mr. S. A. Sklaroff
for help with statistics.
Part of the work was supported by a grant from the
Scottish Hospital Endowments Research Trust.
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The effect of corticotrophin and
corticosteroids on the external
secretion of the pancreas in dogs
Wilfred Sircus
Gut 1961 2: 338-345
doi: 10.1136/gut.2.4.338
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