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The total corticosteroid concentrations in the peripheral plasma of unanaesthetized, undisturbed quokkas were 0·75 ± 0·10 (s.e.m.) and 0·93 ± 0·14 μg/100 ml in male and female quokkas respectively. Repeated sampling for periods of 36–49 h disclosed irregular fluctuations over the range 0·4–5·0 μg/100 ml, but no evidence for a regular periodicity. The major corticosteroid was usually cortisol but corticosterone contributed 25–50% of the total unstimulated corticosteroid concentration. Relatively minor concentrations of 11-deoxycortisol were detected.
Constant-rate i.v. infusion of ACTH caused a significant increase in the concentration of total corticosteroids in the plasma; this increase was detectable at a dose of 0·05 i.u. ACTH/kg/h, and rose to approximately 15 times the control value at a dose of 2·0 i.u./kg/h. This increase was due mainly to a change in the concentration of cortisol. Synthetic (β1–24) and porcine ACTH were equipotent. The sensitivity of the quokka to ACTH was approximately one-tenth that of another marsupial (Trichosurus vulpecula) or 1/160 that of man.
Moderate disturbance increased the concentration of corticosteroids in the plasma to the same level as that caused by infusion of 0·1 i.u. ACTH/kg/h, the increase being mainly in the cortisol fraction. High-affinity binding of cortisol and corticosterone by plasma proteins was demonstrated. The maximum binding capacities for cortisol were 3·89 ± 0·5 and 3·02 ± 0·6 μg/100 ml in female and male quokkas respectively. The mean association constant was 3·2 × 1081/mol at 4 °C and 5·5 × 1071/mol at 36 °C. The maximum binding capacity for corticosterone was approximately one-third that of cortisol.
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In spite of the importance of prolactin and adrenal corticosteroids in the normal control of the mammary gland (Cowie & Tindal, 1971) there has been no report of their simultaneous measurement in rat plasma during pregnancy and lactation. There is no agreement on the pattern of change in corticosteroid concentration at the time of lactogenesis and parturition (Gala & Westphal, 1965; Kuhn, 1969).
Primiparous CFE strain rats, allotted randomly to groups on day 0 of pregnancy, were decapitated without prior disturbance within 1 min after removal from their cage, between 08.30 and 09.30 h. Plasma was stored at −20 °C, total body weight after bleeding and adrenal weight were recorded. The day on which a vaginal plug was found and the day of parturition were designated day 0 of pregnancy and lactation respectively. Litter size was adjusted to six on day 0 of lactation.
Plasma prolactin concentration was assayed in
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Search for other papers by J. SPENCER-PEET in
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SUMMARY
Simple fluorimetric methods for the determination of corticosteroids are not sufficiently specific to allow the accurate estimation of low concentrations in plasma.
It has been noted previously and is confirmed here, that the measured fluorescence is not proportional to the volume of plasma used, but includes a component which is relatively independent of the plasma volume extracted. This gives rise to a positive intercept on the fluorescence axis when fluorescence intensity is plotted against volume.
The suggestion that the determination of plasma corticosteroids can be made specific by subtracting the value of this intercept from the measured fluorescence intensity of the plasma sample has been examined. In the light of experimental data and certain theoretical considerations presented here, this suggestion is rejected.
It is concluded that the inaccuracy due to interfering fluorogens can be reduced by taking fluorimeter readings within 5 min. of extraction into the fluorescence reagent, but that even then specificity is not complete.
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Search for other papers by P. K. BRIDGES in
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In earlier studies (Bridges & Jones, 1967, 1968) we found a significant relationship between adrenocortical responses to the psychological stress of an oral university examination (2nd M.B. Anatomy examination) and body-build, assessed by means of phenotyping by the method of Parnell (1958). This assumes three basic components of physique: fatness (F), muscularity (M) and linearity (L). It was found that the mean plasma corticosteroid concentration at the time of the examination was significantly greater in the primarily linear group than in the mainly muscular students, and there was a significant negative correlation between the examination corticosteroid values and the muscularity scores (r = − 0·225; P < 0·05). One explanation for these findings would be that the muscular group was characterized by a lower sensitivity of adrenocortical response. It was decided to test this possibility using the methods of Landon, James, Wharton & Friedman (1967).
For the present study, 38 students
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Search for other papers by S. R. STITCH in
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SUMMARY
Adrenal tissue from newborn anencephalic infants converted pregnenolone and progesterone to cortisol, 17α-hydroxyprogesterone, corticosterone, 17α,21-dihydroxyprogesterone, deoxycorticosterone and 1 1β-hydroxyprogesterone in vitro. These metabolites were identified by recrystallization to constant specific activity after multiple chromatography and derivative formation. The results demonstrate a potential for corticosteroid biosynthesis, at least from pregnenolone and progesterone, by the adrenals of the anencephalic infant, and therefore possibly by the definitive zone of the adrenal of the normal newborn infant.
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Anti-inflammatory therapy in asthma is reliant on corticosteroids, particularly in their inhaled form. However, steroids are rather non-specific in their actions and they also raise concerns regarding compliance and side-effect Issues. Furthermore, a small proportion of patients with asthma fail to respond to oral glucocorticoids even at high doses. This Article will review the role that steroids and membrane receptor ligation play in the induction of eosinophil apoptosis together with the mechanisms by which corticosteroids enhance the disposal of apoptotic eosinophils by both professional and non-professional phagocytes. Eosinophils are thought to be the major pro-inflammatory effector cell in asthma and their persistence in the airways is probably enhanced by the presence of several asthma-relevant cytokines that prolong eosinophil survival by inhibition of apoptosis (interleukin (IL)-3, IL-5, granulocyte-macrophage colony-stimulating factor, IL-9, IL-13, IL-15). In contrast, a number of signals have been described that accelerate apoptosis in human eosinophils including corticosteroids or ligation of membrane receptors (CD95, CD45, CD69). Thus, the load of lung eosinophils in asthmatic disease is likely to be related to a balance in the tIssue microenvironment between pro- and anti-apoptotic signals. Furthermore, removal of apoptotic eosinophils by phagocytosis by alveolar macrophages or bronchial epithelial cells in a specific receptor-mediated way is as important as the process of apoptosis induction. Corticosteroids enhance the recognition and engulfment of apoptotic eosinophils by macrophages or bronchial epithelial cells. Caspases are key intracellular molecules in the control of apoptosis and defects in caspase-induced apoptosis in eosinophils from steroid-resistant individuals may contribute to the molecular mechanisms underlying glucocorticoid insensitivity in these cells. These findings point the way to new and more targeted anti-inflammatory therapy for asthma and may provide important clues for the development of alternative therapies for glucocorticoid resistance.
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SUMMARY
Adrenal venous and peripheral blood was collected from five adult and two immature kangaroos, anaesthetized with pentobarbitone.
Seven C-21 Δ4, 3-oxo steroids were identified in extracts of adrenal venous blood from all animals. The major component—72–92% of detected corticosteroids—was cortisol. The remainder were 11-deoxy and 21-deoxy cortisol, corticosterone, aldosterone, 11β-OH and 17α-OH progesterone. In four out of six experiments, i.v. corticotrophin caused variable degrees of increase in corticosteroid secretion. Maximum cortisol secretion rates in all the adults and the immature male were in the range 29–70 μg./hr./100 mg. adrenal, or 28–58 μg./hr./kg. body weight and 98 μg./hr./100 mg. or 114 μg./hr./kg. in the immature female.
Average aldosterone secretion rate in the adults was 0·27 μg./hr./100 mg. adrenal, or 0·18 μg./hr./kg. body weight. It was significantly higher in the immature male. However, the Na status of the animals was not known.
Cortisol was the major corticosteroid in peripheral blood plasma at concentrations of 2·0–8·1 μg./100 ml.
The unusual secretion of 21-deoxy cortisol suggests there may be differences in some aspects of adrenocortical biosynthesis, compared with eutherians.
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SUMMARY
Copulation with an oestrous sow or exposure to an aggressive boar resulted in a sharp rise in the concentration of corticosteroids in the plasma of boars, and subsequently, an immediate increase in the concentration of testosterone. Placing a test boar in close proximity to an oestrous sow for a period of 10 h caused three peaks in the concentration of corticosteroids in the plasma, each of which preceded a peak testosterone concentration. An inhibitor of 11 β-hydroxylation, metyrapone, was administered intravenously to limit corticosteroid production. One injection of 5 mg metyrapone/kg body weight or three injections of 4 mg metyrapone/kg body weight did not interfere with the response of the testes to stimulation by luteinizing hormone or human chorionic gonadotrophin. Peak values in the concentrations of corticosteroids and testosterone in the plasma after injection of adrenocorticotrophic hormone were limited to approximately one half when metyrapone was given. Similarly, metyrapone treatment reduced the response, in terms of plasma steroid levels, when test boars were exposed to an oestrous sow or an aggressive boar. The results show that an increase in the concentration of testosterone in the plasma during sexual or aggressive behaviour in the boar is highly correlated with an increase in the concentration of corticosteroids.
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SUMMARY
The influence of several corticosteroids on stress-induced secretion of adrenocorticotrophin was studied. Two periods of inhibition were demonstrated. Fast feedback occurred within minutes with small doses of corticosterone, and was of short duration which was further curtailed as the dose of corticosterone was raised. Delayed feedback occurred after 1 h or later, required larger doses and the duration of inhibition was increased with increased dosage. Corticosterone and cortisol were agonists on both fast and delayed feedback. However, 11-deoxycorticosterone and 11-deoxycortisol were antagonists on fast feedback but agonists on delayed feedback. It is concluded that the two feedback mechanisms have different dynamics and separate receptors.
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Search for other papers by O. STEENO in
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SUMMARY
The previously reported method (De Moor, Steeno, Raskin, Hendrikx & De Tremerie, 1959) for the fluorimetric determination of plasma corticosteroids (cortisol plus corticosterone) has been further simplified and compared with two more elaborate methods intended to determine cortisol more specifically (Van der Vies, 1961; Braunsberg & James, 1962). For normal subjects there is a good relation between results obtained by the simplest method and those obtained by the two others. On the other hand, the latter two techniques give less specific fluorescence and higher reagent blanks. The background fluorescence of the simplified assay has been further studied and was found to lie between 1 and 1·5 μg./100 ml.
