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I. K. Martin
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I. R. McDonald
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ABSTRACT

In a study of adrenocortical functions in macropodid marsupials, measurements were made of the effects of ACTH infusion, ether stress and adrenaline infusion on plasma corticosteroid and glucose concentrations in wallabies (Thylogale billardierii) provided with indwelling venous catheters.

The mean plasma total glucocorticoid concentration in undisturbed males and females was 80 ± 5 (s.e.m.) μg/l, of which more than 90% was cortisol. This fraction declined to 68% of the total at the highest ACTH-stimulated concentration of 225 μg/l, due to an increase in the contribution by 11-deoxycortisol.

Although maximal ACTH stimulation (4·5 i.u./kg per h) caused a five- to sixfold increase in cortisol secretion rate, as measured by isotope dilution during constant-rate tracer infusion, plasma cortisol concentration rose only two- to threefold, due to a marked increase in metabolic clearance.

Plasma glucose concentration did not change significantly during either short-term (1 h) i.v. infusion or long-term (8 days) i.m. injection of ACTH, even though plasma cortisol concentration was significantly increased.

Ether anaesthesia caused a marked hyperglycaemia that preceded an increase in plasma cortisol concentration and was not sustained while plasma cortisol concentration continued to increase.

Infusion of adrenaline i.v. at rates sufficient to cause a similar hyperglycaemia had no significant effect on plasma cortisol concentration. A marked hyperglycaemia during xylazine anaesthesia was not associated with an increase in plasma cortisol concentration and was attributable to suppression of insulin secretion.

It is concluded that, as in the red kangaroo (Macropus rufus) and the quokka (Setonix brachyurus) and in contrast to the reported effects in the tammar wallaby (Macropus eugenii), neither ACTH, nor the increase in plasma glucocorticoid concentration caused by ACTH administration, influence plasma glucose concentration in Thylogale billardierii.

J. Endocr. (1986) 110, 471–480

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I. K. Martin
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I. R. McDonald
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ABSTRACT

In undisturbed pademelon wallabies (Thylogale billardierii) with indwelling jugular venous catheters, an increase in the plasma cortisol concentration from 0.25±0.05 to 1.35±0.15 (s.e.m.) μmol/l in 2 h, during i.v. infusion of cortisol at 1.0 mg/kg per h, caused no significant change in the plasma glucose concentration from the control value of 4.26±0.25 mmol/l. The rates of appearance (Ra) and metabolic clearance (MCR) of glucose, measured by steady-state isotope dilution, also did not change significantly from the control values of 14.9±0.7 μmol/kg per min and 3.52±0.19 ml/kg per min respectively. Twice-daily i.m. injections of 7 mg cortisol/kg for 7 days caused increases in plasma concentrations of cortisol, from 0.26±0.02 to 0.66±0.04 μmol/l on day 7, and glucose, from 5.1±0.1 to 7.2±0.6 mmol/l by day 5. The concentration of glycogen in the liver of wallabies fasted for 24 h increased from the control level of 1.17±0.56 to 5.92±1.14 g/100 g on day 7 (P<0.01), but mean glucose Ra and MCR did not change significantly. Plasma concentrations of α-amino nitrogen rose from 2.73±0.13 to 3.22±0.12 mmol/l on day 1 and remained at this level. Plasma concentrations of urea rose from 8.59±0.62 to 9.70±0.32 mmol/l on day 1, but then declined below the control level. Food intake and urinary excretion of nitrogen did not change in undisturbed animals. However, fasting followed by liver biopsy was accompanied by urinary excretion of nitrogen in excess of food intake, persisting until day 2 of treatment.

The transient effect of cortisol on the plasma concentration of urea and lack of effect on urinary excretion of nitrogen could be explained by urea recycling, as indicated by a low urinary urea nitrogen: total nitrogen ratio and failure to excrete more than a mean of 26% of infused urea.

It is concluded that cortisol has no short-term effect on carbohydrate metabolism in this marsupial. In the long term it can increase hepatic carbohydrate reserves through utilization of tissue amino nitrogen, the resulting urea being conserved by recycling.

J. Endocr. (1988) 116, 71–79

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R. W. Danby
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I. K. Martin
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W. R. Gibson
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The effects of pancreatectomy and of injection of insulin or tolbutamide on glucose fluxes in chickens were examined. This was prompted by earlier observations that tolbutamide seems not to require the presence of pancreatic insulin for its acute hypoglycaemic action in this species. Rates of appearance (Ra) and disappearance (Rd) of glucose were estimated by isotope dilution using [14C]glucose in single-injection experiments and [14C]glucose and [6−3H]glucose in priming-injection + constant-infusion experiments.

Six hours after sub-total pancreatectomy (splenic lobe remained in situ), chickens were hyperglycaemic (16·7 v. 10·4 mmol glucose/l in controls), had a larger sampled glucose pool (4·41 v. 3·10 mmol) and a higher average rate of glucose utilization (41·7 v. 33·3 μmol/kg per min) than sham-operated controls as estimated in single-injection experiments. Tolbutamide (50 mg/kg injected i.v.) reduced Ra in intact chickens from 33·9 to 1·1 μmol/kg per min and reduced Ra in pancreatectomized chickens from 42·2 to 10·2 μmol/kg per min. In priming-injection + constant-infusion experiments tolbutamide again reduced Ra significantly. In all cases Rd tended to fall, apparently as a result of the developing hypoglycaemia. Tolbutamide did not affect the volume of extracellular fluid (sucrose space). In single-injection experiments, insulin (1 unit/kg injected i.v.) reduced Ra by 56% and transiently increased Rd by 39%.

It was concluded that pancreatectomy and injection of insulin or tolbutamide produce responses in glucose movements in chickens that are qualitatively similar to those in mammals. In chickens the hypoglycaemic action of tolbutamide, which persists in the absence of the pancreas, depends on an inhibition of glucose release by the liver.

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J. B. BROWN
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K. J. CATT
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F. I. R. MARTIN
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SUMMARY

A procedure for extracting both gonadotrophin and growth hormone from acetone-dried pituitary powder in a form suitable for clinical use is described. Gonadotrophin is extracted first and fractionated by ethanolic precipitation; growth hormone is then extracted from the residues by a modification of Raben's procedure. The yields and potency of the products are given with particular emphasis on their activities in man. The economy of the preparation of gonadotrophin and growth hormone from human pituitaries is discussed.

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I. R. McDonald
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A. K. Lee
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K. A. Than
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R. W. Martin
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ABSTRACT

In an investigation of the factors leading to the increase in the concentration of plasma free glucocorticoid, which results in immunosuppression and death after mating of all males in natural populations of a small shrew-like marsupial, the dusky antechinus (Antechinus swainsonii), the integrity of the glucocorticoid feedback control of the concentration of plasma cortisol was examined by use of dexamethasone-suppression tests.

Injection of 0·2 mg dexamethasone/kg i.m. caused a marked fall in the concentration of plasma cortisol 17 h later, approximately 2 months and 2 weeks before the annual mating period in mid-July. However, the same dose had no significant effect on the increased concentration of plasma cortisol characteristic of the mid- to late July mating period.

Injection of 100 i.u. ACTH/kg i.m. caused a significant increase in the concentration of plasma cortisol 6–7 h later on all occasions, indicating that the responsiveness of the adrenal cortex to ACTH did not change. Pretreatment with dexamethasone had no effect on the ACTH-stimulated cortisol concentration, ruling out a possible direct effect of dexamethasone on adrenocortical secretion in this species. Dexamethasone also reduced the concentration of plasma testosterone when the level was low, before the mating period, but not when the level was high, at the beginning of the mating period.

It is concluded that, in association with a rapid increase in the concentration of plasma testosterone, an increase in aggression and intense mating activity, glucocorticoid feedback control of ACTH secretion is impaired. This contributes to the rapid and sustained rise in the concentration of plasma free cortisol to immunosuppressive levels.

J. Endocr. (1986) 108, 63–68

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S. K. Abbas
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D. W. Pickard
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D. Illingworth
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J. Storer
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D. W. Purdie
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C. Moniz
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M. Dixit
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I. W. Caple
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P. R. Ebeling
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C. P. Rodda
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T. J. Martin
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A. D. Care
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ABSTRACT

A radioimmunoassay based on an antiserum to human parathyroid hormone-related protein PTHrP(1–16) was used with PTHrP(1–34) standard to measure the concentration of immunoreactive PTHrP in extracts of fetal parathyroid glands from lambs and calves and also placental membranes obtained from several species, including man. Dilution curves from these sources were parallel to those obtained for PTHrP(1–34) standard. It was demonstrated that this parallelism was not the result of tracer damage caused by enzymic activity in the tissue extracts. Extracts of human placental membranes were subjected to high-pressure liquid chromatography with a linear acetonitrile gradient. Co-elution of cytochemical biological activity with 125I-labelled PTHrP(1–34) was noted. These results provide further evidence for both the fetal parathyroid glands and the placenta containing material resembling PTHrP which may be responsible for sustaining the activity of the placental calcium pump which maintains the fetus hypercalcaemic relative to its mother.

Journal of Endocrinology (1990) 124, 319–325

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