Download The Effect of Glucagon on Plasma Adenosine 3`:5`

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Medical Research Society
The following hormones were assayed in gradient fractions
and shown to have distinct distributions at the following equilibrium densities: TSH, p = 1.22; p r o l a c t h , ~= 1.23; GH,p =
1.24; LH, p = 1.25; FSH, p = 1.25. Only small amounts
((20%) of the hormones were recovered in the soluble fractions
indicating good maintenance of granule integrity during the
fractionation procedure.
The technique has been applied to specimens from patients
with either prolactin-secreting or GH-secreting turnours. The
principal subcellular organelles had similar distributions to those
in control tissue but prolactin and growth hormone showed a bimodal distribution with approximately half the activity in a
granule at p = 1.16 as well as the normal peak at p = 1.231.24. The combination of analytical subcellular fractionation
with enzymic analysis and hormone measurement can be used
to study the physiological properties of human pituitary cells
and may also be used to investigate the subcellular pathology in
pituitary turnours.
44. THE EFFECT O F GLUCAGON ON PLASMA ADENOSINE 3':5'TYCLIC MONOPHOSPHATE IN PATIENTS
WITH THYROID DISEASE, BEFORE AND AFTER
TREATMENT
S. TOMLINSON,
P. R. DAGGETI and G. N. HENDY
Department of Chemical Pathology, University of Shefield
Medical School, Shefield and Department of Medicine, The
Middlesex Hospital, London
We have previously shown that small doses (10-150 pg) of
intravenous glucagon cause a dose-dependent increase in plasma
adenosine 3':5'-cyclic monophosphate (cyclic AMP) concentration in normal man. In patients with thyroid disease it has
been shown that there is an alteration in this response when
large doses ( I mg) of glucagon are injected: there is an enhanced response in patients with thyrotoxicosis and a
diminished response in patients with myxoedema. We have investigated the glucagon-induced changes in plasma cyclic AMP
in response to a small dose (50pg) of the hormone in patients
with thyroid disease before and after treatment. Eleven hyperthyroid patients and four hypothyroid patients were studied. The
mean basal concentration of plasma cyclic AMP was higher in
thyrotoxic patients (25.9 nmol/l) than in patients with myxoedema (19.4 nmol/l) in whom the concentration was normal.
After an injection of glucagon plasma cyclic AMP reached a
mean peak value of 392 nmol/l (range 150-990 nmol/l) in
patients with thyrotoxicosis compared with 132 nmol/l (range
68-225 nmol/l) in hypothyroid patients. In eight normal subjects a mean peak value of 176 nmol/l (range 8 1-344 nmol/l)
occurred after an injection of this dose of hormone. There was
therefore an enhanced response in patients with thyrotoxicosis
and a diminished response in patients who had myxoedema, but
with some overlap between the groups.
However, three patients with thyrotoxicosis were given an
injection of the same dose of hormone when they were clinically
and biochemically euthyroid after treatment. In each patient the
plasma cyclic AMP response to the hormone had diminished
with successful treatment: one patient had a peak response of
280 nmol/l before treatment and 150 nmol/l after treatment, in
another the peak response fell from 340 nmol/l to 140 nmol/l
with treatment and in the third it fell from 310 nmol/l to 220
nmol/l. In contrast, in one patient with myxoedema tested before
and after thyroxine therapy had begun the peak response
increased from 55 nmol/l to 110 nmol/l.
Therefore, in patients with thyroid disease there appears to be
an alteration in the target tissue response to glucagon that is
reversible with treatment. It is possible that this phenomenon
could be useful in monitoring therapy when tests of thyroid
secretory function can sometimes be unreliable.
45. THE EFFECT O F LITHIUM A N D RUBIDIUM
ON THE RESPONSE TO ANTIDIURETIC HORMONE AND PARATHYROID HORMONE IN THE
RAT
S. JOHNSON,
G. JENNINGS'and S. MACNEILL
Department of Chemical Pathology, University of Shefield
Medical School, Beech Hill Road, Shefield, and *MRC Unit
f o r Metabolic Studies in Psychiatry, Middlewood Hospital,
She#eld
Although lithium is of established value in the treatment of
periodic psychoses, rubidium is at present still being evaluated.
Lithium can cause certain endocrine side-effects in man,
possibly by the inhibition of hormone-stimulated adenylate
cyclase. It was decided therefore to investigate whether
rubidium might have similar side-effects by studying the action
of two hormones, antidiuretic hormone (ADH) and parathyroid hormone (PTH) in rats given lithium or rubidium in
their diet.
Animals received diet mixed 1 : 1 with 30 mmol/l solutions of
NaCl (control group), LiCl or RbCl for 14 days. Animals were
then anaesthetized with ethanol and water-loaded and the antidiuretic effect of ADH and the phosphaturia and increase in
urinary cyclic AMP induced by PTH were then measured.
Rubidium had no effect on the antidiuretic response to ADH
but lithium reduced the response from a maximum 74.9 ? 3.0%
reduction in urine flow in the control group to 16.6 k 4.3% in
the lithium group.
In the control group there was a relationship between the
phosphaturic and the cyclic AMP response to PTH ( P < 0.05)
which was not apparent in animals that had received lithium or
rubidium. Both lithium and rubidium reduced the degree of
PTH-induced phosphaturia but this was correlated with a reduction in the basal phosphate excretion. In these experiments the
phosphaturic response to PTH was clearly dependent on the
basal phosphate excretion. Lithium caused a slight but nonsignificant reduction in the cyclic AMP response to PTH but
rubidium increased this from a total of 9.62 2 1.12 nmol to
13.39 -t 1.1 I nmol ( P < 0.05) in the 40 min post-injection.
Rubidium has no effect on ADH action but potentiates the
cyclic AMP response to PTH. Lithium on the other hand
appears not to affect PTH action but clearly inhibits target
organ response to ADH.
46. QUANTITATIVE
HISTOCHEMICAL
EXAMINATION OF HUMAN ARTICULAR CARTILAGE DURING
AGEING
R. J. ELLIOITand D. L. GARDNER
Department of Histopathology, University of Manchester, South
Manchester Teaching Hospital, West Didsbury, Manchester
Human femoral condyle articular cartilage sections were stained
with Safranin 0 in water, Alcian Blue at pH 2.5 in 3% acetic
acid and Alcian Blue at pH 5.8 with 0.2 and 0.8 M-MgCI,. The
stained sections were examined by a quantitative densitometric
procedure. Two staining patterns were observed: (a) a cartilage
zonal-dependent dyematrix distribution and (b) cartilage agedependent dye-matrix changes within the cartilage zones (Table
1).
I n cartilage sections in the age range 0-70 years (34 specimens) the surface zone (0-50 pm) contained the least
chromogen. With increasing distance from the surface the
chromogen concentration increased; this pattern was detected
with the Safranin 0 and Alcian Blue-0.2 M-MgCI, reagents.
The Alcian B W 0 . 8 M-MgCI, stained sections revealed a small
linear increase in chromogen concentration with increasing
depth from the cartilage surface (0-1 mm).
Age-associated patterns in the stained sections were not as
distinct, or as consistent, as the zonal chromogen patterns. With
Safranin 0 and Alcian Blue/O.Z M-MgCI, small changes in