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JEAN-PIERRE BARLET
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MICHEL THERIEZ
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I.N.R.A., Theix, 63110 Beaumont, France

(Received 17 October 1975)

Calcitonin deficiency (induced by thyroidectomy) has been shown to be associated with a wasteful loss of calcium in the urine in rats (Munson, Cooper, Gray, Peng, Toverud, Harper & Ontjes, 1973) and goats (Barlet & Garel, 1975). In the work reported here, we have investigated the influence of calcitonin (CT) on renal calcium and phosphate content in lambs.

In the first experiment thirteen 2-month-old weaned (22-24 kg body wt) female lambs were used. Seven of them had been surgically thyroidectomized (TX) (the upper parathyroid glands being left intact) 10 days before the beginning of the experiment. Five days after the operation these seven TX lambs were supplemented with thyroxine (T4) (200 μg/animal/day) so that plasma hormonal iodine levels were not statistically different in TX (3·10 ± 0·47 (s.e.m.) μg/100 ml) and in intact control animals (3·27 ± 0·58 μg/100ml). During the experimental period (40 days) each animal ingested 6 g calcium, 2 g magnesium and 9 g phosphate daily. At the time of slaughtering, the right kidney of each animal

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A. WRIGHT
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J. G. PHILLIPS
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D. P. HUANG
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SUMMARY

Domestic ducks were adenohypophysectomized and 2–3 weeks later were loaded with hypertonic saline. Normal intact ducks and sham-operated ducks were similarly treated. For 2 hr. nasal gland secretion was almost completely inhibited (0·20 g.) in the adenohypophysectomized ducks and was significantly reduced (4·93 g.) in the sham-operated ducks compared with the normal intact controls (14·74 g.).

When the renal response of the adenohypophysectomized ducks was compared with that of the normal intact controls no significant difference was found as far as volume of urine and concentration of Na+ and K+ were concerned. When compared with sham-operated controls, however, these values were significantly lower in adenohypophysectomized ducks.

The adrenal weight was not significantly reduced in the adenohypophysectomized ducks, but the weights of thyroid, nasal gland and testis decreased significantly. Histological examination of the adrenal glands of the adenohypophysectomized ducks showed that the central regions were atrophic while the peripheral regions remained normal. Nasal glands, thyroid glands and testes were also examined.

It is concluded that the adenohypophysis plays a major part in regulating extrarenal excretion.

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CH Verhoelst
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S Van Der Geyten
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VM Darras
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Iodothyronine deiodinase in vitro activity studies in the chicken showed the presence of type I and type III iodothyronine deiodinase activity in both liver and kidney. Due to the lack of a specific antiserum the cellular localization of the deiodinase proteins could not be revealed until now. In the present study, specific antisera were used to study the renal and hepatic distribution of type I and type III iodothyronine deiodinase protein in the chicken. Immunocytochemical staining of liver tissue led to an immunopositive signal in the hepatocytes in general. Moreover, a zonal distribution could be detected for both enzymes. Maximum protein expression was shown in a thin layer of hepatocytes bordering the blood veins. Although pericentral localization of type I deiodinase protein has been previously reported in the rat, no data were given concerning type III deiodinase protein. In the present study, we report the co-localization of both enzymes in the chicken. Co-expression of the deiodinases was also found in the kidney. Expression of both proteins was associated with the tubular epithelial cells and with the transitional epithelium, and the inner longitudinal and outer circular muscle layers of the ureter. No staining could be detected in the lamina propria or in the fat tissue surrounding the ureter.

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J. R. J. BAKER
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H. P. J. BENNETT
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R. A. CHRISTIAN
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C. McMARTIN
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Renal resorption of tritiated adrenocorticotrophin analogues was studied in the rat using light microscopic and quantitative electron microscopic autoradiography. The synthetic corticotrophins used were Synacthen (corticotrophin-(1–24)-tetracosapeptide) and C 41795-Ba ([D-Ser1,Lys17,Lys18]-corticotrophin-(1–18)-octadecapeptide amide), the tetracosapeptide being tritiated in either the tyrosine residue of position 2 or 23 or the phenylalanine of position 7 and the octadecapeptide in the tyrosine of position 2. Inspection of autoradiographs showed that peptides injected intravenously were resorbed into proximal tubules by endocytosis to produce vesicles whose radiolabel later appeared in lysosomes, a route previously elucidated for other peptides and proteins. The use of two techniques for analysis of electron microscopic autoradiographs, however, suggested that apical tubules also acquire label and are in some way involved in the transfer of resorbed labelled material from endocytotic vesicles to lysosomes. In addition, the autoradiographic analyses revealed that the duration of lysosomal labelling depends upon the position of tritium in the chain. Thus, when the CO2H-terminus of Synacthen was labelled, silver grains were more transiently associated with lysosomes than was the case when the NH2-terminal or core regions were tritiated, indicating a greater resistance of these portions of the peptide to attack by intracellular peptidase. The label from the chemically protected C 41795-Ba was also less readily expelled from the lysosomes of the proximal tubules.

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S. PORS NIELSEN
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B. BUCHANAN-LEE
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E. W. MATTHEWS
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J. M. MOSELEY
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C. C. WILLIAMS
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SUMMARY

Synthetic porcine calcitonin (α-calcitonin) and its methionine-sulphoxide derivative (β-calcitonin) were given by intravenous infusion to conscious male rats. α-Calcitonin inactivated by performic acid oxidation was used as a control.

Microgram doses of α-calcitonin produced a dose-dependent decrease in the renal excretion of magnesium. The effect was not due to a secondary release of parathyroid hormone since it was also seen in parathyroidectomized animals.

A marked increase in the renal excretion of inorganic phosphate, sodium and potassium preceded the change in magnesium excretion in parathyroidectomized rats. It is concluded that the phosphaturia and natriuresis previously described after administration of extracted calcitonin preparations are true effects of the hormone.

The effect of β-calcitonin was indistinguishable from that of α-calcitonin.

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B. A. PANARETTO
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J. Y. F. PATERSON
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F. HILLS
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SUMMARY

The uptake of cortisol by organs in the splanchnic area of conscious, undisturbed sheep was estimated before and during the administration of adrenocorticotrophic hormone (ACTH) by measuring cortisol concentration differences in portal and hepatic venous plasma and estimating hepatic plasma flow rates. Metabolic clearance rates (MCR) of plasma cortisol were measured simultaneously. The total splanchnic clearance of cortisol was 61% of MCR in the animal, 48% being accounted for by the liver. When ACTH was given there were increases in MCR and these were accompanied by proportional increases in hepatic plasma flow rates. When ACTH was infused the total splanchnic clearance rate was 65% of MCR, 52–59% being accounted for by the liver.

In other experiments the renal clearance rate of cortisol was studied. Under control conditions, and when ACTH was given, the renal clearance was 11% of MCR.

The relationship of the sum of individual clearances to MCR is compared and discussed.

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E. MIDDLETON
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P. C. WILLIAMS
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SUMMARY

Male guinea-pigs were studied in individual metabolism cages for 6–12 weeks before, and for 13 weeks after, subcutaneous implantation of stilboestrol (15 mg). They were fed on cabbage and either normal pelleted diet (SG1) or sodium-enriched SG1, and had access to either water or to water and 0·86% saline. In all, 42 control and experimental animals were studied and renal function tests were made at 3-week intervals in 18 of them.

The treated animals lost appetite and weight but increased their fluid intake; they showed a preference for saline when this was available and, in doing so, reduced their polydipsia. Fluid and sodium balances were unaffected. The increased sodium appetite, whether satisfied or not, was accompanied by a fall in faecal sodium excretion and a rise in faecal potassium excretion. Renal function tests in themselves also produced some increase in sodium appetite, but no changes in faecal electrolyte excretion. These results suggest strongly that the mechanisms involved in the stimulation of sodium appetite by stilboestrol and renal function tests are different, partly because of the differences mentioned above, but also because the effects of the two procedures when combined were almost exactly additive.

The increased sodium appetite of the treated animals was not explicable by changes in renal function: inulin and creatinine clearances were only slightly reduced and concentrating ability unimpaired. This increased appetite may well be the result of adrenocortical stimulation by stilboestrol acting via extrarenal means.

No change in potassium appetite was observed, possibly because the potassium content of the diet was in excess of requirement. There was a seasonal variation in potassium balance which was lowest in summer in control and treated animals.

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ROBERT FRASER
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V. H. T. JAMES
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J. J. BROWN
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D. L. DAVIES
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A. F. LEVER
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J. I. S. ROBERTSON
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SUMMARY

A woman with recurrent urinary infection, bilateral renal calculi, and an abnormal pattern of plasma proteins was unable to reduce urinary sodium excretion when sodium intake was restricted.

When the intake of sodium was reduced depletion developed rapidly, and severe hyponatraemia was associated with increased plasma renin and aldosterone concentrations, and a less marked although definite, increase in plasma corticosterone. Plasma cortisol was unchanged during sodium depletion, although it increased normally after the administration of corticotrophin.

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D. CULLIFORD
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H. B. HEWITT
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SUMMARY

1. Adult male mice of two strains developed extensive necrosis of the renal tubules after exposure to low concentrations of chloroform vapour. Adult females showed no renal damage after equivalent exposures.

2. Adult females became fully susceptible to necrosis after treatment with androgens. The susceptibility of males was greatly reduced by treatment with oestrogens.

3. Castration removed the susceptibility of the males in one strain but did not completely remove it in another. The residual susceptibility of castrates was abolished by adrenalectomy.

4. Male mice under 11 days old were insusceptible to necrosis even after massive doses of androgen. Between 11 and 30 days they were susceptible if given androgen. Thereafter they became spontaneously susceptible.

5. Liver damage occurred in nearly all exposed mice and was not correlated with sex hormone status.

6. Susceptibility could be induced in gonadectomized mice by methyl testosterone, testosterone propionate, dehydroepiandrosterone and progesterone, and by large doses of cortisone acetate.

7. Preliminary exposure to carbon tetrachloride completely protected susceptible males against renal damage by chloroform.

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M Dodic
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M Tersteeg
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A Jefferies
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EM Wintour
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K Moritz
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Low-dose dexamethasone treatment is used in pregnancies where the fetus is suspected to be at risk of congenital adrenal hyperplasia (CAH). In order to see if such treatment had long-term effects, pregnant ewes were treated with dexamethasone (20 micro g/kg maternal body weight) or saline from 25 to 45 days of gestation and blood pressure and renal function studied in offspring at 2 Years of age. There were 11 animals from dexamethasone treatment (six females and five males) and nine lambs from saline treatment (five females and four males). We aimed to study blood pressure and heart rate in the adult animals of both genders, and renal function only in the adult female animals.In both females and males, blood pressure and heart rate were similar between the two groups of animals. The excretion rates of sodium and potassium were similar between the two groups of animals. In addition, glomerular filtration rate was not different between the two groups of animals (112+/-11 ml/kg per h (S.E.M.) in saline-treated females vs 112+/-10 ml/kg per h in dexamethasone-treated females). There were no differences in body weight or weights of the kidney and heart between the treatments in both females and males.In conclusion, these results are reassuring for patients similarly exposed to prenatal dexamethasone treatment for CAH, as in our animal model no evidence of altered renal function or predisposition to adult hypertension was found.

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