Studies on the carbohydrate metabolism of sheep. XI. The role of the adrenals in ovine pregnancy toxaemia

1960 ◽  
Vol 11 (3) ◽  
pp. 364 ◽  
Author(s):  
RL Reid

Plasma cortisol levels in fed and fasted non-pregnant and in undernourished pregnant ewes were consistently less than 1.5 µg per 100 ml. Most values were considerably above this level in 20 field cases of pregnancy toxaemia, 31 of 52 values being greater than 3 µg per 100 ml. These levels must be regarded as abnormally high in sheep. Pregnancy toxaemia was induced in two experiments by fasting after a period of severe under nutrition and in two by fasting previously well-nourished ewes in the presence of severe psychological stresses. The onset of clinical signs was associated with marked increases above normal in plasma cortisol. In three experiments involving a total of 23 previously well-nourished ewes, 11 of which carried twins or triplets, only one mild case of pregnancy toxaemia was induced by complete fasting in late pregnancy for up to 6 days, in the absence of any additional environmental stress. Pregnancy toxaemia was readily induced in 24 of 38 ewes in three experiments when severe psychological stresses accompanied fasting in late pregnancy. Adrenal hypertrophy, indicating sustained adrenal hyperactivity, was most pronounced in field cases of pregnancy toxaemia induced primarily by sustained under nutrition. Fresh adrenal weights (total of two adrenals) averaged 6.7 g compared to 3.8 g in normal non-pregnant ewes. Mean plasma cortisol levels in ewes with pregnancy toxaemia were significantly correlated with fresh adrenal weight. The suggestions that abnormalities of carbohydrate and fat metabolism in ewes with pregnancy toxaemia are those of adrenal steroid diabetes, and that cerebral depression may be largely a consequence of a cortisol-induced inhibition of glucose utilization, are discussed in the light of the probable metabolic effects of cortisol in the undernourished pregnant ewe.

1960 ◽  
Vol 11 (3) ◽  
pp. 346 ◽  
Author(s):  
RL Reid

Data on blood glucose, ketone, and acetic acid values have been obtained over a period of several years from field cases of pregnancy toxaemia and from cases induced experimentally and their controls. When feed intake is controlled, differences between blood glucose and ketone levels in ewes moderately undernourished in late pregnancy are largely dependent on the number of foetuses. The consistency of these differences often allows accurate diagnosis of multiple and single pregnancies. Differences in blood glucose between undernourished monotocous and polytocous ewes disappear when undernutrition becomes severe or in the early stages of fasting after a period of moderate undernutrition. Differences in blood ketones tend to be maintained even after several days of fasting. The level of blood ketones during fasting depends on the previous level of nutrition of the ewe; blood glucose is unaffected by previous level of nutrition. The frequent presence of persistent normoglycaemia in ewes with pregnancy toxaemia is discussed in the light of data presented; it is concluded that the onset of pregnancy toxaemia often occurs in the presence of normal blood glucose levels. Blood volatile fatty acid (V.F.A.) levels are often high in those cases of pregnancy toxaemia which occur largely as a result of severe under nutrition in late pregnancy, in spite of an almost empty rumen. Only acetic acid was detected in six blood samples examined; this is considered to be of metabolic origin, but there is no consistent relationship with blood ketone level. The usual clinical syndrome of pregnancy toxaemia can be classified as acute or subacute. In the latter, cerebral depression reaches a certain stage of severity which is then maintained, survival is often prolonged, and ewes do not become comatose before death. Cases of pregnancy toxaemia induced by under nutrition alone usually show the acute syndrome. Blood ketones are higher in such cases than in fasted ewes showing no clinical signs; the critical blood ketone level appears to be about 30 mg per 100 ml. Cases induced in previously well-nourished ewes by fasting in association with a severe environmental stress are usually subacute; blood ketones are no higher than in ewes not showing clinical signs and are often considerably below 30 mg per 100 ml. The significance of these observations is discussed.


1965 ◽  
Vol 64 (1) ◽  
pp. 11-14 ◽  
Author(s):  
N. Saba

Pregnancy toxaemia in ewes is a metabolic disorder which may occur during the last month of pregnancy. Typical symptoms are anorexia, hypoglycaemia, hyperketonaemia, blindness, ataxia and recumbency. The condition usually proves fatal. Reid & Hogan (1959) have put forward the suggestion that pregnancy toxaemia is an adrenal steroid diabetes. However, pregnancy toxaemia in ewes is generally associated with starvation or severe undernutrition, and McClymont & Setchell (1955) have suggested that under these conditions the symptoms of pregnancy toxaemia are due to cerebral depression caused by hypoglycaemia. As part of investigations on pregnancy toxaemia, adrenal steroid metabolism in ewes was studied. This paper presents data on plasma cortisol levels during the last month of pregnancy in ewes, and the possible effects of undernutrition and cold on these levels.


1968 ◽  
Vol 19 (4) ◽  
pp. 555 ◽  
Author(s):  
Graham N McC

The nitrogen metabolism of five non-pregnant ewes and 16 pregnant ewes was studied. The aim was to examine the effects of pregnancy on the response to severe undernutrition. Some measurements of energy metabolism and blood composition were also made. Pregnant ewes excreted less urea nitrogen in the urine than did non-pregnant ewes when they were all well fed. When food intake was reduced by 75%, excretion by the non-pregnant ewes declined, whereas excretion by the pregnant ewes declined less or increased. After 5 days on the lower ration, pregnant ewes excreted up to 9 g more urea nitrogen daily than did non-pregnant ewes. Urea clearance was constant throughout and was 30–40% of creatinine clearance. Undernutrition caused hypoglycaemia and hyperketonaemia in the pregnant ewes only but there were no clinical signs of pregnancy toxaemia. The heat production of pregnant ewes declined when their ration was reduced. The estimated heat increment of pregnancy was greater with the reduced ration than with the large ration and it is suggested that this change represented the energy cost of gluconeogenesis and ketogenesis from protein. The gross energy content of protein apparently oxidized was estimated to be about 20% of the energy requirement of the foetus. The effects of pregnancy on nitrogen and energy metabolism and on response to undernutrition were approximately proportional to the birth weight of the lamb, and were smaller 7 weeks before lambing than 2 weeks before lambing.


1971 ◽  
Vol 50 (1) ◽  
pp. 75-96 ◽  
Author(s):  
J. N. BALL ◽  
I. CHESTER JONES ◽  
M. E. FORSTER ◽  
G. HARGREAVES ◽  
E. F. HAWKINS ◽  
...  

SUMMARY The competitive protein-binding radioassay (CPB method) of Murphy (1967) has been adapted to determine total cortisol levels in the plasma of the eel, Anguilla anguilla L. Validation of the method for this species depended in part on the development of a chromatographic—fluorimetric technique for eel cortisol, following classical procedures and using radioactive tracers; by this means, the specificity of the CPB method for cortisol in eel plasma was established. Accuracy, precision and sensitivity of the CPB method were also investigated and were shown to be satisfactory. Plasma total cortisol levels were determined in eels during osmotic adjustments after transfers from fresh water (FW) to sea-water (SW) and vice versa, and from FW to distilled water. Plasma osmotic pressure and/or sodium levels were monitored simultaneously, to follow the progress of osmotic regulation. In only one of the transfer situations did the plasma cortisol level change significantly, showing a marked transitory increase during the first few days after transfer from FW to SW, corresponding to the development and correction of an 'osmotic crisis'. Plasma cortisol levels were the same in eels adapted for long periods to FW and to SW. Plasma cortisol fell to extremely low levels after hypophysectomy. These results are discussed in the light of the literature on hormonal control of osmoregulatory mechanisms in the eel, with particular emphasis on the role of adrenocorticosteroids in ionic regulation of animals in SW.


1978 ◽  
Vol 87 (4) ◽  
pp. 820-827 ◽  
Author(s):  
G. Reck ◽  
H. Nowostawskyj ◽  
M. Breckwoldt

ABSTRACT The present study is concerned with the role of maternal cortisol in regulating diurnal rhythm of unconjugated oestriol in 9 pregnant women. Blood was drawn at 30 min intervals between 5 p. m. and 3 a. m. In 5 patients endogenous ACTH-secretion was simultaneously suppressed by 12 mg dexamethasone over 48 h. Between 8 p. m. and 2 a. m., 0.25 mg ACTH1-24 (Synacthen®) was infused into the subjects. Free oestriol was measured by radioimmunoassay, and the total plasma cortisol by the protein binding method. Patients without dexamethasone demonstrated high oestriol levels (21.5 ± 9 ng/ml) and episodic secretion between 5 p. m. and 8 p. m. At the same time cortisol concentrations were relatively low (274.1 ± 66 ng/ml). Ninety min after starting ACTH-infusion, plasma oestriol decreased in negative correlation to rising cortisol (r = −0.916, P < 0.001). Between 11 p. m. and 2 a. m. oestriol levels were significantly below the control values (12.9 ± 3 ng/ml, P < 0.001) and were associated with high cortisol levels (887 ± 312 ng/ml). Episodic oestriol production did not occur during the period of elevated cortisol levels. Under dexamethasone both oestriol (2.1 ± 1.2 ng/ml) and cortisol values (36.5 ± 24 ng/ml) were markedly suppressed. Only cortisol production could be stimulated during ACTH-infusion (374 ± 80 ng/ml), whereas oestriol concentration remained in the range of the controls (1.91 ± 0.5 ng/ml). These results suggest that diurnal rhythm of unconjugated oestriol is predominantly regulated by feed-back action of maternal cortisol on the foetal hypothalamus.


1960 ◽  
Vol 11 (1) ◽  
pp. 42 ◽  
Author(s):  
RL Reid

The rate of utilization of injected glucose by fasted pregnant ewes or ewes with pregnancy toxaemia is much more rapid than by fasted non-pregnant ewes. An apparent relation between the rate of utilization and the number of fetuses was observed; much of the injected glucose may be removed by the foetus(es). The pronounced rise in blood glucose recorded after lambing and when foetuses apparently died in utero is also considered to reflect sudden cessation of high foetal demands for glucose. Intravenous administration of glucose consistently reduced blood ketones in ewes with a moderate hyperketonaemia and showing no clinical signs of pregnancy toxaemia. Ketones declined in ewes fasted 1–3 days as soon as blood glucose began to increase at lambing. In ewes with pregnancy toxaemia there was usually no reduction of ketones in response to injected glucose; blood acetic acid levels, if previously high, did not decline; blood citric acid failed to increase. Glycerol given per os to ewes with pregnancy toxaemia always caused a rapid decline in blood ketones, and in acetic acid if the latter was previously high; a, pronounced increase in blood citric acid always occurred. These changes were recorded although no clinical improvement was observed. Glucose administered parenterally over 48 hr appeared to be less efficiently utilized by ewes with pregnancy toxaemia than by fasted pregnant ewes showing no clinical signs. Blood ketones declined to normal levels within 48 hr; in probable contrast to fasted ewes, this is considered to have occurred in the ewes with pregnancy toxaemia only because hyperglycaemia was continuously maintained. These results are considered to support the hypothesis that gluoose metabolism is depressed in ewes with pregnancy toxaemia and that the metabolic abnormalities are consistent with those characteristic of a diabetic-like syndrome.


2019 ◽  
Vol 104 (11) ◽  
pp. 5065-5072 ◽  
Author(s):  
Manon Engels ◽  
Karijn J Pijnenburg-Kleizen ◽  
Agustini Utari ◽  
Sultana M H Faradz ◽  
Sandra Oude-Alink ◽  
...  

Abstract Context and Objective We describe the clinical features and biochemical characteristics of a unique population of severely affected untreated patients with congenital adrenal hyperplasia (CAH) from an Indonesian population with proven cortisol deficiency but without clinical signs of cortisol deficiency. We evaluated the in vitro glucocorticoid activity of all relevant adrenal steroid precursors occurring in patients with CAH. Design Cross-sectional cohort study and translational research. Intervention/Main Outcome Measures Adrenal steroid precursor concentrations before and 60 minutes after ACTH administration to 24 untreated patients with CAH (3 to 46 years) with proven cortisol deficiency (<500 nmol/L post-ACTH) measured by liquid chromatography–tandem mass spectrometry were compared with six control patients (Mann-Whitney U test). Glucocorticoid receptor (GR) activation was determined by dual-luciferase assays in human embryonic kidney cells transfected with the GR and exposed to increasing amounts of adrenal steroid precursors for 24 hours. Results Blood concentrations of the steroid precursors 11-deoxycortisol (457 nmol/L, P = 0.003), 11-deoxycorticosterone (55 nmol/L, P = 0.003), 17-hydroxyprogesterone (610 nmol/L, P < 0.001), progesterone (29 nmol/L, P < 0.001), and 21-deoxycortisol (73 nmol/L) were strongly elevated compared with control subjects. The GR was activated with comparable potency to cortisol by corticosterone and 21-deoxycortisol or with 4 to 100 times lower potency by 11-hydroxyprogesterone, 11-deoxycortisol, aldosterone, 11-deoxycorticosterone, progesterone, and 17-hydroxyprogesterone. Conclusions We identified strongly elevated adrenal steroid precursor concentrations in blood from untreated patients with CAH and demonstrated glucocorticoid activity of these adrenal precursors in vitro, suggesting a possible role of these precursors in the clinical phenotype of these patients. Further studies are necessary to evaluate the role of these precursors in more detail.


1963 ◽  
Vol 27 (1) ◽  
pp. 21-30 ◽  
Author(s):  
R. L. REID ◽  
N. T. HINKS

SUMMARY The effects of insulin, glucose injection and oral glycerol on blood or plasma levels of glucose, free fatty acids (FFA), acetic acid and ketone bodies have been studied in alloxan-diabetic sheep. Insulin (0·5 i.u./kg.) lowered glucose levels only slightly, but induced a prompt and marked fall in FFA and acetate levels; ketones declined steadily after the first hour. The rate of utilization of injected glucose was considerably slower in diabetic than in non-diabetic sheep. FFA levels did not decline after glucose injection, while acetate levels declined slowly. Ketone levels were not affected significantly. Glycerol (180 ml.) per os reduced acetate and ketone levels, while tending to increase FFA values. Blood glucose also increased considerably. These data are consistent with present knowledge of the metabolic lesions in severe diabetes. However, it is concluded that there is impairment of acetate and, probably, ketone oxidation in severe diabetic ketosis. Finally, the metabolic changes recorded are compared with those which occur after insulin, glucose or glycerol administration to ewes showing clinical signs of ovine pregnancy toxaemia following severe and prolonged undernourishment in late pregnancy.


1980 ◽  
Vol 87 (3) ◽  
pp. 455-461 ◽  
Author(s):  
A. EL HANI ◽  
M. DALLE ◽  
P. DELOST

Sexual dimorphism in adrenal activity appeared during the pubertal period of the guinea-pig with plasma levels and binding of cortisol lower in male guinea-pigs compared with female, and metabolic clearance rate (MCR) of cortisol higher in male than in female animals. Gonadectomy of female guinea-pigs did not change the values of the parameters regulating adrenal activity. Castration of male guinea-pigs caused a rise in plasma cortisol levels by increasing the binding capacity of transcortin for cortisol and by decreasing cortisol MCR. Treatment of females with testosterone from day 24 produced a drop on day 50 in plasma cortisol levels following a decreased binding capacity of transcortin for cortisol and at the same time as cortisol MCR increased. Furthermore, the adrenal response to stress was higher in castrated than in control males and lower in testosterone-treated females compared with control females. Testosterone appeared to be the hormone responsible for sexual dimorphism in adrenal activity in the pubertal guinea-pig.


1973 ◽  
Vol 74 (2) ◽  
pp. 331-337 ◽  
Author(s):  
D. C. Thurley ◽  
K. P. McNatty

ABSTRACT Sheep were bled at frequent intervals over a period including cyclical oestrus activity, pregnancy and lactation. The changes in peripheral plasma cortisol levels in response to herding by better or less well trained dogs or by people were compared. In all cases the cortisol response took the form of a hump-backed curve. The height of this hump was lower when people drove the sheep than when dogs were used, and was lower during lactation than in late pregnancy.


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