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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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W. R. GIBSON
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B. K. FOLLETT
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BARBARA GLEDHILL
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SUMMARY

Plasma levels of luteinizing hormone (LH) were measured by radioimmunoassay in gonadectomized male and female Japanese quail, exposed either to 8 h light: 16 h darkness per day (8L:16D; short days) or to 20L:4D (long days). In both sexes, exposure to long days increased LH levels and in the gonadectomized quail LH continued to rise over several weeks. Eventually the castrated quail had levels about five times higher than the control birds and the ovariectomized quail had levels about 14 times higher than their controls.

Quail kept on short days had low LH levels while birds kept on long days and returned to short days resumed low levels after a delay of some days. Since very high levels of LH occurred in gonadectomized quail only when they were on long days, we conclude that the photoperiodic regulation of LH secretion does not operate solely by adjusting sensitivity to gonadal feedback, but works in a more direct manner.

Ovariectomized females whether on long days (high LH) or short days (low LH) grew masculine plumage and castrated males retained male plumage. This confirms that the ovary is responsible for sexual dimorphism of plumage and shows that the action of the ovary is not mediated by LH (through feedback).

The remaining rudimentary (right) gonad in ovariectomized females did not undergo visible hypertrophy and did not secrete enough hormone to stimulate the cloacal gland or oviduct.

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S. R. Crosby
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M. F. Stewart
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W. E. Farrell
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S. Gibson
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A. White
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ABSTRACT

The molecular forms of ACTH secreted by established human small cell lung cancer (SCLC) cells and primary cultures derived from a bronchial carcinoid tumour, a pituitary adenoma and hyperplastic pituitary tissue have been characterized by Sephadex G-75 chromatography and quantified with two novel immunoradiometric assays for ACTH and ACTH precursor peptides. Pro-opiomelanocortin (POMC; M r 31 000) and pro-ACTH (M r 22 000) were secreted by all cell types. No smaller peptides were identified in the culture media from SCLC and bronchial carcinoid cells, implying a deficiency in the enzymes and/or intracellular organelles required for extensive POMC processing. A more heterogeneous profile of ACTH-containing peptides was produced by cells of pituitary origin, indicating more extensive proteolytic processing of POMC. However, the major peptide secreted by cells from a large aggressive pituitary adenoma was unprocessed POMC (M r 31 000). These results suggest that both lung and pituitary cells in vitro retain their in-vivo pattern of POMC processing and provide valuable models in which to study the regulation of ACTH synthesis and secretion.

Journal of Endocrinology (1990) 125, 147–152

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David E Henley Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine, Clinical Biochemistry, University of Bristol, Bristol BS1 3NY, UK
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine, Clinical Biochemistry, University of Bristol, Bristol BS1 3NY, UK

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Fiona Buchanan Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine, Clinical Biochemistry, University of Bristol, Bristol BS1 3NY, UK

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Rosemary Gibson Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine, Clinical Biochemistry, University of Bristol, Bristol BS1 3NY, UK

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Jennie A Douthwaite Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine, Clinical Biochemistry, University of Bristol, Bristol BS1 3NY, UK

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Susan A Wood Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine, Clinical Biochemistry, University of Bristol, Bristol BS1 3NY, UK

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Wolfram W Woltersdorf Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine, Clinical Biochemistry, University of Bristol, Bristol BS1 3NY, UK

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James R Catterall Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine, Clinical Biochemistry, University of Bristol, Bristol BS1 3NY, UK

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Stafford L Lightman Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine, Clinical Biochemistry, University of Bristol, Bristol BS1 3NY, UK

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Apelin is a peptide hormone with cardiovascular and glucose homeostasis properties, and obstructive sleep apnea (OSA) is complicated by cardiovascular and metabolic comorbidities. Plasma apelin has not been previously assessed in OSA. We investigated the response of plasma apelin to a 2-h 75 g oral glucose tolerance test (OGTT) and the effect of 3 months compliant continuous positive airway pressure (CPAP) therapy in 15 obese males with newly diagnosed OSA. Plasma apelin and serum cortisol were recorded 10 minutely, while serum insulin and glucose were measured 30 minutely. Ten subjects had plasma apelin measured at intervals across a 24-h period to investigate for circadian variation in apelin levels, and this was repeated following 3 months compliant CPAP therapy. Fasting (0.342±0.038 vs 0.288±0.024 ng/ml, P=0.04), 30 min (0.399±0.035 vs 0.312±0.036 ng/ml, P=0.007) and 120 min (0.402±0.030 vs 0.259±0.024 ng/ml, P<0.001) apelin levels were reduced following CPAP. The area under curve for apelin OGTT response was lower post-CPAP (44.1±3.3 vs 35.8±2.3 ng/ml per min, P<0.001). Mean OGTT apelin levels showed a significant treatment effect (P=0.006) and a time effect (P<0.001), and the effect of time was different pre- versus post-CPAP (P=0.005). No significant variability in apelin levels existed across the 24-h period at diagnosis. Lower levels were evident overnight following treatment (P=0.004). Improvements in insulin and glucose parameters and reduced cortisol levels were found post-CPAP. In summary, untreated OSA was associated with elevated plasma apelin levels, altered apelin secretory dynamics in response to oral glucose and lack of an apparent circadian variability, which was restored following CPAP.

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J. R. BLAIR-WEST
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J. P. COGHLAN
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D. A. DENTON
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ANGELA P. GIBSON
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CATHERINE J. ODDIE
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W. H. SAWYER
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B. A. SCOGGINS
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Plasma renin activity (PRA) and blood aldosterone and deoxycorticosterone levels were measured in Australian lungfish. Plasma renin activity was depressed after intravenous infusions of iso-osmotic (0·6%) NaCl but not after hypo-osmotic (0·3%) infusions. The presence of PRA in this fish is consistent with prior reports of renal renin activity in other sarcopterygian fishes. The results of the infusion experiments suggest that a fall in plasma osmolality or electrolyte concentrations may oppose the reduction in renin release in response to volume expansion.

Aldosterone and deoxycorticosterone were identified in the blood of Neoceratodus. The concentrations of both appeared higher in females than in males. Infusions of [5-valine]-angiotensin II amide for 2–4 h at rates known to increase blood pressure in this species did not alter blood aldosterone concentrations. This negative finding may suggest that the renin/angiotensin system is not involved in aldosterone regulation in Neoceratodus or that angiotensin receptors involved in regulation of steroidogenesis have a greater specificity for endogenous angiotensin than do vascular receptors.

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