Plasma Corticosteroid Concentrations Research Articles

Relation between corticosteroid and albumin concentrations in umbilical vein plasma and the duration of labour.

The concentration of corticosteroids in the umbilical vein plasma of babies delivered after a spontaneous onset of labour showed a significant positive correlation with the duration of labour (r=0-593; P less than 0-001) and the length of the second stage (r=0-48; P less than 0-02). Similar results were also obtained for induced labours. For labours of both induced and spontaneous onset, the albumin concentration in cord plasma also correlated significantly (r=0-46; P less than 0-01) with the corticosteroid concentration. It is concluded that the stress of labour and vaginal delivery, and possibly changes in the concentration of proteins which bind corticosteroids, are impoertant in determining the corticosteroid concentration in cord plasma obtained after delivery of the baby. The significance of these findings in relation to mechanisms responsible for the onset of human labour is discussed.

DEVELOPMENTAL CHANGES IN THE RESPONSES OF THE ADRENAL GLANDS OF FOETAL SHEEP TO ENDOGENOUS ADRENOCORTICOTROPHIN, AS INDICATED BY HORMONE RESPONSES TO HYPOXAEMIA

The change in plasma ACTH and corticosteroid concentrations in response to a 60 min period of hypoxaemia were studied in foetal and adult sheep during the latter half of pregnancy. Hypoxaemia consistently caused large rises in the concentration of ACTH in foetal plasma, the magnitude of which did not change with gestational age but was related to the physiological state of the foetus. Before 139 days small and slow rises in corticosteroid (predominantly cortisol) concentration in foetal plasma were observed during hypoxaemia, and these may have been of maternal origin. After 139 days, hypoxaemia caused a rapid and large rise in the concentration of cortisol and corticosterone in foetal plasma, which was largely of foetal origin. Hypoxaemia caused no consistent change in maternal plasma ACTH concentration but was associated with progressive increases in plasma cortisol concentrations. The cortisol: corticosterone ratio in foetal plasma was 1-5 before 139 days and increased to 4-1 several days before term which was lower than the value of 9 in maternal plasma. Small concentrations of 11-deoxycortisol and cortisone were detected in maternal and foetal plasma, the changes of which were small during hypoxaemia. The results indicate that a maturational change in the sensitivity of the foetal adrenal to endogenous ACTH occurs several days before term.

CHANGES IN THE CONCENTRATION OF ADRENOCORTICOTROPHIN AND CORTICOSTEROID IN THE PLASMA OF FOETAL SHEEP IN THE LATTER HALF OF PREGNANCY AND DURING LABOUR

The changes in plasma ACTH concentration of pregnant sheep and their foetuses during the latter half of pregnancy and during labour were studied. Before 140 days of gestation the mean concentration in foetal arterial plasma was 117+/-19 (S.E.M.) pg/ml which rose to a mean of 286+/-63 pg/ml. The rise in ACTH occurred at about the same time as, but not before, the rise in corticosteroid concentration in foetal plasma. The maternal plasma ACTH concentration did not change during the latter half of pregnancy and had a mean concentration of 64+/-9 pg/ml. During labour there was a progressive rise in the ACTH concentration in foetal plasma which was not associated with any corticosteroid changes. Ethanol did not suppress labour but reduced the ACTH concentration in foetal plasma.

Effect of angiotensin II and glucocorticoids on plasma angiotensinogen concentration in the dog.

The increase in plasma angiotensinogen concentration produced by angiotensin II infusion in the dog is accompanied by an increase in plasma corticosteroid concentration and is prevented by adrenalectomy. The present study was undertaken to test the possibility that the angiotensinogen response to angiotensin is mediated via an increase in glucocorticoid secretion. Infusion of angiotensin II (3-6 mug/h for 5 h) into the third cerebral ventricle of five dogs increased plasma corticosteroid concentration from 3.5+/-0.6 to 11.8+/-1.5 mug/dl (P less than 0.025) but did not increase plasma corticosteroid concentration from 2.7+/-0.4 to 7.8+/-1.5 mug/dl (P less than 0.05) but again failed to increase plasma angiotensinogen concentration. On the other hand, more prolonged glucocorticoid treatment with dexamethasone produced a significant increase in plasma angiotensinogen concentration within 24 h. Intravenous infusion of angiotensin II (50 mug/h for 5 h) in five acutely hypophysectomized dogs receiving a cortisol infusion caused only a small increase in plasma corticosteroid concentration (5.0+/-0.5 TO 6.9+/-0.6 mug/dl, P less than 0.02) but increased plasma angiotensinogen concentration from 967+/-122 to 1,358+/-204 ng/ml (P less than 0.02). These results indicate that although glucocorticoids can increase plasma angiotensinogen concentration, the angiotensinogen response to angiotensin II is not dependent on increased glucocorticoid secretion.

The effects of bilateral adrenalectomy or hypophysectomy of the foetal lamb in utero.

1. Foetal hypophysectomy or bilateral adrenalectomy, carried out in utero at about 100 or 125 days gestation respectively, increased the length of gestation in sheep. It was confirmed that pregnancy was not prolonged significantly if hypophysectomy or adrenalectomy was carried out on one of a pair of twins. The hypophysectomized foetus was, however, smaller and the adrenalectomized foetus larger, than the unoperated twin. 2. In about half of the previously operated foetuses intravascular catheters were inserted into both mother and foetus, either at about 125 days, for a comparison with normal catheterized foetuses, or during the post-mature period. Both adrenalectomized and hypophysectomized foetuses appeared to have little resistance to stress or infection and the majority survived only 1-2 weeks after the insertion of catheters. 3. Maternal peripheral plasma oestrogen, progesterone and corticosteroid concentrations did not appear to be altered by either foetal hypophysectomy or adrenalectomy and were maintained in the normal range during prolonged gestation. 4. Foetal plasma oestrogen concentrations were significantly lower after hypophysectomy or adrenalectomy than values found in control lambs. Plasma progesterone values were low in all three groups of foetuses. 5. Plasma corticosteroid concentrations after foetal hypophysectomy (12-6 ng/ml.) or adrenalectomy (14-7 ng/ml.) were in the same range as the values for control lambs before the pre-partum rise (14-6 ng/ml.). However, there was a small but significant maternal-to-foetal plasma corticosteroid gradient in the two operated groups whereas this difference was not found in the control animals. 6. Tissue glycogen concentrations were measured in non-catheterized adrenalectomized and hypophysectomized foetuses. In these two groups, whether examined before 149 days or after prolonged gestation, liver glycogen concentrations were 30-40% of those in non-catheterized control foetuses at term. In other respects there was little apparent difference between adrenalectomized and control foetuses. 7. Hypophysectomized foetuses had significantly higher glycogen concentrations in heart, skeletal muscle and lung compared with control or adrenalectomized lambs. Plasma glucose and fructose values were also low in this group compared with control foetuses.

ADRENOCORTICAL FUNCTION IN A PROTOTHERIAN MAMMAL, TACHYGLOSSUS ACULEATUS (SHAW)

The peripheral plasma concentrations and production rates of corticosterone and cortisol were measured in the conscious, unrestrained echidna (Tachyglossus aculeatus) under basal conditions and during maximal ACTH stimulation. Using Sephadex LH-20 column chromatography and radioligand assay, only cortisol and corticosterone could be detected in the peripheral blood plasma at very low concentrations of 0-07 +/- 0-03 (S.E.M.) mug/100 ml and 0-14 +/- 0-07 mug/100 ml respectively. Two-hourly sampling over periods of 36-48 h disclosed a diurnal periodicity in the combined plasma concentration of these corticosteroids, the high concentrations corresponding to periods of behavioural activity. Marked, short-term fluctuations in plasma corticosteroid concentration were also observed during periods of more frequent (20 min) sampling. Constant rate i.v. infusion of synthetic ACTH increased the plasma concentrations of both steroids to maximal values of 0-42 +/- 0-23 mug cortisol/100 ml and 1-06 +/- 0-56 mug corticosterone/100 ml at infusion rates of 1 i.u. ACTH/kg/h. This is approximately 1/160 of the potency of this ACTH in man. The production rates of corticosterone and cortisol, measured by isotope dilution during constant rate i.v. infusion of 3H-labelled tracers, were only 0-35 +/- 0-21 and 0-56 +/- 0-26 mug/kg/h respectively during saline infusion, and increased to 2-86 +/- 3-47 and 2-74 +/- 2-07 mug/kg/h during the infusion of 1 i.u. ACTH/kg/h. The metabolic clearance rate of cortisol was greater than that of corticosterone and both were depressed by ACTH. Plasma corticosteroid concentrations were increased after surgery during ether anaesthesia and in sick animals with heavy worm infestation. It is concluded that the adrenal cortex of echidnas responds to ACTH stimulation and stress in a similar way to eutherians, but the level of activity is much lower.

Relationship between foetal corticosteroids, maternal progesterone and parturition in the rat.

ABSTRACT The concentration of total corticosteroids, corticosteroid binding globulin (CBG) and progesterone were determined in maternal and foetal/neonatal plasma from rats on days 5, 4, 3, 2, 1 before birth and days 0, 1, and 4 after birth. In addition free corticosteroids and adrenal weight/unit body weight were measured on the foetuses/neonates and the foetuses, respectively. Although the concentration of maternal total corticosteroids and CBG ranged from 53.0 ± 12.5 to 31.0 ± 13.1 μg/100 ml (x̄ ± sem) and 26.6 ± 2.2 to 45.1 ± 0.9 μg corticosteroid bound/100 ml plasma, respectively, the changes in the concentration of these constituents were not related to the initiation of either parturition or lactation. The concentration of total corticosteroids in foetal plasma increased significanly (P < 0.05) from day 5 (14.6 μg/100 ml) to reach peak concentrations (44.9 μg/100 ml) on day 3 before birth and then decreased to low levels (7.7 μg/100 ml) at birth. The pattern of change in foetal adrenal weight/unit body weight closely followed the pattern of change in the concentration of total corticosteroids in foetal plasma during the last 5 days of gestation. There was a significant (P < 0.05) daily decrease in the concentration of CBG in the foetuses from 4 days before until 1 day before birth, which resulted in a significant (P < 0.01) increase from 3.08 to 5.94 μg/100 ml of free corticosteroids in the foetal plasma between day 2 and day 1 before birth, respectively. This peak corresponded with a significant fall (P < 0.02) in the maternal progesterone (measured by protein binding assay) from 2.57 μg/100 ml to 0.62 μg/100 ml between day 2 and day 1 before birth. Foetal progesterone (measured by radioimmunoassay) showed the same changes as maternal progesterone but was between 25–50 % of that in maternal plasma. These findings suggest that the changes in foetal free corticosteroids and maternal progesterone are important in the initiation of parturition in the rat.

Early effects of diquat on plasma corticosteroid concentrations in rats

Plasma corticosteroid concentrations were significantly elevated 15 min after intraperitoneal (i.p.) injection of 90 μmoles of diquat/kg body wt (ld50 dose) into phenobarbitone anaesthetised rats. Similar effects were noted after subcutaneous dosing but after oral administration there was a delay of approximately 1 hr before significantly elevated concentrations were observed. The magnitude of the increase after i.p. administration of diquat was dose-related up to 26 μmoles/kg body wt, as was the duration of the response. The increase in plasma corticosteroid concentration in diquat-treated rats could be prevented by pretreating animals with dexamethasone which also reduced adrenocorticotrophic hormone (ACTH) concentration in these animals. Experiments in vivo and in vitro indicated that diquat did not increase the steroidogenic response of adrenals to ACTH. It is concluded that the increased adrenal steroid synthesis observed at early times after diquat administration is caused by release of ACTH from the pituitary.

Daily Variation in Concentration of Plasma Corticosteroid in Hypophysectomized Rats

A daily variation in the concentration of plasma corticosteroid hormone is present in hypophysectomized rats implanted with pellets of adrenocorticotropic hormone (ACTH) and thyroxine. Although ACTH is necessary to maintain a functional adrenal, and thyroxine is required to permit the expression of the plasma corticosteroid rhythm, a normal daily variation in plasma corticosteroid concentration does not appear to depend on the periodic release of pituitary hormones.

Detection and Characterization of Differences in Plasma Corticoid Response to Treatments

Ten experiments involving 3013 observations and 103 animals were studied to characterize variation associated with bovine plasma corticoid concentrations (ng/ml). Total corticoids, corticosterone, or cortisol were measured by competitve protein binding assay. Animals were noncystic or cystic, and measurements were made to establish basal concentrations or to estimate response to stimulation by adrenocorticotrophic hormone injection. Data were analyzed by least squares with the nested model: treatment regimen, animal in treatment, sample in animal in treatment, and sampling time to the highest order of regression (up to seventh) which was statistically significant (P less than .05). Estimates of error variances ranged from .31 for basal cortisol in cystic animals to 233.27 for total corticoids in noncystic, stimulated animals. Coefficients of variation among experiments ranged from 33 to 87% with mean 61%. In most analyses, estimates of experimental error were large indicating need for careful attention to experimental design to insure efficient least-cost experimentation. Use of the power function for nested analysis of variance to accomplish this is demonstrated.

Some behavioural and physiological changes in pregnant goats and sheep during adaptation to laboratory conditions

Eight goats and 12 sheep were examined during their first six to eight weeks in the laboratory. Plasma corticosteroid concentrations in four untamed goats and four untamed sheep were elevated during the first week but thereafter remained at basal values. In contrast, low corticosteroid concentrations were observed throughout in four tame goats and in four untamed sheep sampled only after they had been in the laboratory for two weeks. Plasma glucose concentrations were elevated during the first week in the untamed goats. In four partially tamed sheep a rise in heart rate which occurred transiently during handling for 4-6 min did not occur when these animals showed tame behaviour after two to three weeks, and in four untamed sheep a rise in plasma corticosteroid concentration, which occurred transiently when seven blood samples were taken in 90 min, did not occur when these sheep were judged to be tame after five to six weeks.

Plasma Corticoid Levels During Early Postnatal Life in Calves

There do not appear to be data available on plasma levels of aldosterone and progesterone in the newborn calf. Previous studies on plasma corticoid concentration in the neonate of this species have been confined to the measurement of 17-hydroxycorticosteroids (1-4). In addition, evidence as to whether the calf is born with an adequate or poor supply of circulating adrenocorticoids is controversial. In this regard, several studies (2-4) have shown in normal neonatal calves that plasma cortisol levels vary with age, with the highest concentration seen during the first day following birth. Furthermore, these data (2-4) indicated that the initial high levels of plasma cortisol decreased toward the adult concentration within the next few days. Moll (5), however, favors the view that calves are born with immature adrenals and thus are poorly equipped to cope with environmental changes. There is also disagreement as to whether corticosterone is present in plasma at birth (2, 6). The present study was, therefore,...

Age dependent changes in body weight, haematocrit and corticosteroids following sequential castration in rats with a high incidence of spontaneous tumours

Body weight, packed red cell volume and plasma corticosteroid concentrations were measured at 4–5 week intervals in male and female Sprague-Dawley rats up to 48 weeks old and in males between 113 and 136 weeks old. Similar parameters were measured in both sexes up to 48 weeks old following castration at ages between 1 and 43 weeks old. The effects of castration were sex dependent. In males body weight was less than in controls, haematocrit was increased in groups castrated at 4 and 7 weeks old, and except for the group castrated at 4 weeks old corticosteroid concentration was increased in groups castrated prior to 20 weeks old. In females body weight increased in groups castrated prior to 20 weeks old, haematocrit was increased in groups castrated prior to 33 weeks old (except for the group castrated at 24 weeks old) and castration had no effect on corticosteroid concentrations. Sex differences existed between controls in body weight and haematocrit (males > females) and corticosteroid concentration (females > males); the difference in haematocrit was abolished after castration and indicates a role of the gonads in determining haematocrit levels. Age dependent changes are described for controls and castrates. In general body weight increased with age and only decreased in the old rats during the last weeks of life; corticosteroid concentration and haematocrit initially increased with age in females and castrates of both sexes and they showed little further change with age.

Hormonal Regulation of Renal Ornithine Decarboxylase Activity in the Rat1

The regulation of the activity of the renal enzyme ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) was examined in the rat. In the intact animal adapted to a light/dark cycle of 14 hours and 10 hours, respectively, the level of renal ornithine decarboxylase activity was rhythmical and paralleled the diurnal rhythm in plasma corticosteroid concentration. Renal ornithine decarboxylase activity and plasma corticosterone were highest during the early hours of darkness and lowest during the hours of light. Following hypophysectomy, the level of renal ornithine decarboxylase activity declined rapidly and remained low and without a demonstrable diurnal rhythm. When pituitary hormone levels were temporarily restored in the hypophysectomized rat by the injection of pituitary extract, renal ornithine decarboxylase activity increased rapidly, reached a peak within 8 hours, and returned toward pre-injection levels by 12 hours. Exogenous growth hormone, ACTH and cortisol each increased renal ornithine decarboxylase activity in the hypophysectomized rat, with the highest levels of activity being achieved with growth hormone. Other pituitary hormones (FSH, LH, TSH and prolactin) were ineffective. After bilateral adrenalectomy, renal ornithine decarboxylase activity retained a rhythmical pattern similar to that observed in the intact rat, but the levels were increased. Growth hormone and cortisol increased renal ornitine decarboxylase activity in the adrenalectomized-hypophysectomized animal to the same extent as in the hypophysectomized animal, but ACTH was almost totally ineffective. These data suggest that the pituitary plays a major role in the regulation of renal ornithine decarboxylase activity in the rat, primarily through the rhythmical secretion of growth hormone and ACTH.

Studies on plasma corticosteroids in the rhesus monkey (Macaca mulatta).

The physiological regulation of the plasma corticosteroid concentration, measured by competitive protein-binding, was studied in female rhesus monkeys (M. mulatta) sedated with phencyclidine hydrochloride. Morning basal levels of plasma corticosteroids were found to be in the range 8-0-25-2 mug/100 ml, which is lower than that previously reported in this species. A circadian rhythm in plasma cortisol concentration was demonstrated. Prolonged sedation with phencyclidine was associated with a gradual increase in the plasma cortisol concentration. Synthetic alpha1-24 adrenocorticotrophic hormone given intravenously caused a rapid rise in plasma cortisol, the minimum effective dose was between 1 and 10 ng/kg body weight and the response was maximal after 1000 ng/kg. The administration of lysine-vasopressin and the induction of hypoglycaemia by insulin were both followed by an increase in the plasma corticosteroid concentration. Metyrapone caused a decline in plasma 11-hydroxycorticosteroids and a concomitant increase in total corticosteroids measured by competitive protein-binding. It is concluded that the hypothalamic-pituitary-adrenal system in the rhesus monkey functions in a manner which is qualitatively and quantitatively similar to that of man.

Corticosteroids in brain tissue.

Total corticosteroid concentrations were determined in the plasma and brains of five species: mouse, rat, cat, monkey and man. Corticosteroid concentrations were measured also in the livers of mice, rats and monkeys. Competitive protein binding techniques were validated and used for the tissue corticosteroid assays. In each species the brain corticosteroid value was less than the total plasma corticosteroid level but greater than the presumed unbound fraction of plasma corticosteroids. A clear circadian variation of brain corticosteroid values was found in mice, together with a rapid elevation of the tissue levels in response to stress. Reduction of both plasma and tissue corticosteroid concentrations was observed after adrenalectomy and in response to dexamethasone treatment of mice. Between 24 and 48 h post morten, mouse brain corticosteroid values decreased greatly. In cat, monkey and human brains all regions examined contained approximately equal amounts of corticosteroids. In particular, brain areas which are not involved in pituitary-adrenocortical regulation contained large amounts of corticosteroids.

Husbandry influences on some physiological parameters of emotional responses in calves

Experiments with Jersey calves were designed to monitor changes in heart rate (H.R.) and plasma levels of corticosteroids resulting from experiences encountered under modern routine husbandry practices. Simple restraint and immobilization for venipuncture caused an elevation in H.R. from a resting rate of below 100 beats per minute (b.p.m.) to a rate in excess of 140 b.p.m. A 10 min restraint period induced the maximum increase in plasma corticosteroid concentration, from a resting level of 7.7 ng/ml to 28.8 ng/ml. Drastic reduction in living space for a 14 day period caused only a transient elevation in H.R. and plasma corticosteroid concentration in the period immediately after entering the cubicle. Transportation effects on H.R. and plasma corticosteroids were greater when the calves were transported free than when the same journey was repeated with the calf carried within a wooden cubicle. Recumbency during transportation resulted in a significant lowering of H.R. It is concluded that the wide range of stimuli encountered by calves under normal husbandry practices are capable of inducing varying degrees of emotional responses. These responses seemed to depend largely on the magnitude and degree of novelty inherent in the presented stimulus.

Alteration by drugs of the daily rhythm of plasma corticosteroid concentration in the Gulf killifish, Fundulus grandis

The daily rise in plasma concentrations of corticosteroid that occurs at 8 hr after the onset of a 12-hr daily photoperiod in male Gulf killifish was blocked by injections of atropine, pentobarbital, and physostigmine administered 4 hr previously. Injections of epinephrine, phentolamine, and normal saline were ineffective. These results indicate that the neural regulation of a daily rhythm of plasma corticosteroid involves cholinergic mechanisms.

Plasma corticosteroid concentrations in the bovine fetus near term: Fairclough, R. J., J. T. Hunter, R. A. S. Welch & E. Payne: J. Endocr., [formula omitted](1): 139–140, 1975. Ministry of Agriculture and Fisheries, Ruakura Agricultural Research Station, Private Bag, Hamilton, New Zealand

Plasma corticosteroid concentrations in the bovine fetus near term: Fairclough, R. J., J. T. Hunter, R. A. S. Welch & E. Payne: J. Endocr., [formula omitted](1): 139–140, 1975. Ministry of Agriculture and Fisheries, Ruakura Agricultural Research Station, Private Bag, Hamilton, New Zealand

Effect of postnatal malnutrition on plasma corticosteroid levels in male albino rats.

Basal morning plasma corticosteroid concentrations were significantly elevated in 11 and 21 day old male albino rats suckled by dams receiving a 12% casein diet when compared to control rats suckled by dams receiving a 25% casein diet. Rats which were either well-fed or malnourished during lactation then given a 9% casein after weaning had elevated corticosteroid levels and adrenal hypertrophy at 49 days of age. These changes may be related to altered adrenocortical responsivity found in adult rats malnourished in infancy.