scholarly journals Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

2000 ◽  
Vol 165 (2) ◽  
pp. 527-532 ◽  
Author(s):  
N Picard-Hagen ◽  
V Gayrard ◽  
M Alvinerie ◽  
V Laroute ◽  
C Touron ◽  
...  
Keyword(s):  
Plasma Cortisol ◽  
Binding Capacity ◽  
Equilibrium Dialysis ◽  
Free Fraction ◽  
Biologically Active ◽  
Total Plasma ◽  
Neurodegenerative Process ◽  
Naturally Occurring ◽  
Free Cortisol ◽  
And Control

Naturally scrapie-affected ewes present a syndrome of hypercortisolism as evaluated by measuring total plasma cortisol concentrations. The objective of this study was to investigate the plasma protein binding of cortisol and to evaluate the concentration of the biologically active free fraction of cortisol in scrapie-affected ewes. Corticosteroid binding globulin (CBG) binding parameters were evaluated by equilibrium dialysis in 13 naturally scrapie-affected ewes and nine healthy ewes, during two periods of the clinical evolution of the disease. The hypercortisolism of the scrapie-affected ewes was confirmed by a significant increase of the plasma 20 beta-dihydrocortisol and cortisone concentrations, while total cortisol concentrations, obtained from an isolated sample, did not differ between scrapie-affected and control ewes. The scrapie diagnosis was confirmed by histopathology. The CBG maximal capacity (B(max)) was two times lower in scrapie-affected ewes than in healthy ewes (37+/-32 nM and 73+/-28 nM respectively). The dissociation constant K(d) (8.8+/-3.7 nM and 9.8+/-3.0 nM respectively) and the non-specific constant value of binding to albumin (1.13+/-0.18 and 1.14+/-0.23 respectively) did not differ significantly between diseased and control ewes. The significant increased concentrations of CBG-free cortisol (i.e. both albumin-bound and free cortisol fractions) in scrapie-affected ewes indicates that total plasma cortisol concentration is not an appropriate index of pituitary-adrenocortical hyperactivity. In conclusion, ewes with naturally occurring scrapie display a syndrome of hypercortisolism associated with a lower CBG binding capacity which leads to an overexposure of glucocorticoid-sensitive targets to CBG-free cortisol. The physiopathological consequences of this overexposure on the development of the neurodegenerative process in prion disease are discussed.

scholarly journals A nonlabeled method to evaluate cortisol production rate by modeling plasma CBG-free cortisol disposition

2001 ◽  
Vol 281 (5) ◽  
pp. E946-E956 ◽  
Author(s):  
N. Picard-Hagen ◽  
V. Gayrard ◽  
M. Alvinerie ◽  
H. Smeyers ◽  
R. Ricou ◽  
...  
Keyword(s):  
Production Rate ◽  
Plasma Cortisol ◽  
Specific Binding ◽  
Equilibrium Dialysis ◽  
Total Plasma ◽  
Entry Rate ◽  
Free Cortisol ◽  
Corticosteroid Binding Globulin ◽  
Radioisotopic Method

This study aimed to develop a nonlabeled method for the measurement of cortisol production rate to evaluate adrenal function. The cortisol production rate determination requires that of cortisol clearance, which is not a parameter but a variable resulting from the saturable binding of cortisol to corticosteroid-binding globulin (CBG). Our method is based on evaluation of the plasma clearance of the CBG-free cortisol fraction. This parameter was evaluated from a pharmacokinetic model of total plasma cortisol disposition that takes into account specific binding of the corticoid to CBG in the plasma. We have shown that the CBG-free cortisol kinetics and CBG-binding parameters thus evaluated are not statistically different from those obtained by the radioisotopic method and equilibrium dialysis, suggesting that the plasma CBG-free cortisol clearance is independent of the total plasma cortisol concentrations and represents the actual parameter of cortisol elimination. We validated this modeling approach by using it to calculate the in vivo entry rate of cortisol mimicked by the perfusion of cortisol at a known rate.

PLASMA CORTISOL, CORTICOSTERONE AND NON-PROTEIN-BOUND CORTISOL IN EXTRACORPOREAL CIRCULATION

1972 ◽  
Vol 69 (3) ◽  
pp. 517-525 ◽  
Author(s):  
T. Uozumi ◽  
H. Manabe ◽  
Y. Kawashima ◽  
Y. Hamanaka ◽  
Y. Monden ◽  
...  
Keyword(s):  
Cortisol Level ◽  
Extracorporeal Circulation ◽  
Plasma Cortisol ◽  
Elevated Level ◽  
Marked Decrease ◽  
Binding Capacity ◽  
Biologically Active ◽  
Major Surgery ◽  
Plasma Samples ◽  
Effective Factor

ABSTRACT The response of plasma cortisol, corticosterone and non-protein-bound cortisol in the extracorporeal circulation was investigated in 14 patients. The pre-perfusion levels of plasma cortisol, corticosterone and non-protein-bound cortisol were significantly elevated. During and immediately after perfusion, the levels of cortisol and corticosterone were found to decrease significantly from the pre-perfusion levels, while the percentage of non-protein-bound cortisol was shown to increase significantly. This indicates a marked decrease in cortisol binding capacity of plasma during extracorporeal circulation. Moreover in 200 plasma samples, it was demonstrated that the cortisol level increased markedly and the cortisol binding capacity decreased slightly during and shortly after major surgery without perfusion. It is concluded that stressful situations in major surgery with or without perfusion are associated with markedly increased levels of biologically active non-protein-bound cortisol. The elevated level of non-protein-bound cortisol in surgery seems to be dependent on the increase in the level of plasma cortisol as well as on the decrease in the cortisol binding capacity of plasma. Although the increased plasma cortisol plays the most important role in surgery with no perfusion, the decreased cortisol binding capacity may be the more effective factor involved during perfusion.

Plasma cortisol-binding capacity in mental illness

1973 ◽  
Vol 3 (1) ◽  
pp. 53-65 ◽  
Author(s):  
David J. King
Keyword(s):  
Mental Illness ◽  
Affective Disorder ◽  
Genetic Marker ◽  
Affective Disorders ◽  
Plasma Cortisol ◽  
Binding Capacity ◽  
Psychiatric Patients ◽  
Total Plasma ◽  
Cortisol Levels

SynopsisPlasma cortisol-binding capacity (CBC) was determined in 18 psychiatric patients, including 14 who had affective disorders, and 18 controls. Men with unipolar depressive illnesses had significantly lower CBC values than men with bipolar illnesses and male controls. No other significant differences in CBC values were found and it was concluded that elevated total plasma cortisol levels in affective disorder were probably associated with increased levels of unbound cortisol. The possibility that low CBC values may be a genetic marker for certain types of affective disorder requires further investigation. The effect of certain drugs on CBC was also investigated.

EFFECTS OF SURGERY ON PLASMA LEVELS OF CORTISOL, CORTICOSTERONE AND NON-PROTEIN-BOUND-CORTISOL

1970 ◽  
Vol 64 (3) ◽  
pp. 439-451 ◽  
Author(s):  
Yuji Hamanaka ◽  
Hisao Manabe ◽  
Hideyuki Tanaka ◽  
Yasumasa Monden ◽  
Tohru Uozumi ◽  
...  
Keyword(s):  
Diurnal Variation ◽  
Plasma Levels ◽  
Plasma Cortisol ◽  
Equilibrium Dialysis ◽  
Chronically Ill ◽  
Biologically Active ◽  
Major Surgery ◽  
Corticosterone Concentration ◽  
Control Subjects ◽  
Maximum Value

ABSTRACT The diurnal variation in plasma cortisol, corticosterone and non-protein-bound cortisol was investigated using altogether 991 plasma samples obtained from preoperative chronically ill (control) subjects and patients during and following major surgery. A fluorimetric method using an elution chromatography on Amberlite IRC-50 and the equilibrium dialysis method were used for the determinations. The diurnal variation in plasma cortisol of the preoperative control subjects reached a peak (17.3 μg/100 ml) at 6 a.m. and declined to the lowest level (2.3 μg/100 ml) between 10 p.m. and midnight. The maximum value in the levels of corticosterone (0.6 μg/100 ml) was observed at 6 a.m. Surgery caused a steep rise in plasma cortisol showing a maximum value (30.0 μg/100 ml) 2 to 4 hours after the end of the operation. Although the average of the morning levels of plasma cortisol returned to the control levels within 4 to 5 days, the evening levels returned on the 6th day after the operation. The response of plasma corticosterone in the surgery group was found to parallel the change in plasma cortisol. However, the increase in the corticosterone concentration was significantly higher than that of cortisol. The percentage of non-protein-bound cortisol in the plasma of the preoperative control subjects was found to be 2.5 to 3.3 per cent at 6 and 8 a.m. and 1.5 per cent at midnight, while the percentage remained almost unchanged (about 2%) at 10 a.m., 12 a.m. and 6 p.m. The percentage increased significantly during and for 4 days following the operation, concomitant with the increase in the levels of plasma cortisol. It is suggested that stressful situations are associated with markedly increased plasma levels of biologically active cortisol.

scholarly journals The effect of social stress on adrenal axis activity in horses: the importance of monitoring corticosteroid-binding globulin capacity

1998 ◽  
Vol 157 (3) ◽  
pp. 425-432 ◽  
Author(s):  
SL Alexander ◽  
CH Irvine
Keyword(s):  
Social Stress ◽  
Plasma Cortisol ◽  
Binding Capacity ◽  
Plasma Concentrations ◽  
Social Instability ◽  
Total Cortisol ◽  
Adrenal Axis ◽  
Free Cortisol ◽  
Corticosteroid Binding Globulin ◽  
Cortisol Levels

Plasma cortisol is largely bound to corticosteroid-binding globulin (CBG), which regulates its bioavailability by restricting exit from capillaries. Levels of CBG may be altered by several factors including stress and this can influence the amount of cortisol reaching cells. This study investigated the effect of social instability on plasma concentrations of CBG, total and free (not protein bound) cortisol in horses. Horses new to our research herd ('newcomers') were confined in a small yard with four dominant resident horses for 3-4 h daily for 3-4 (n = 5) or 9-14 (n = 3) days. Jugular blood was collected in the mornings from newcomers before the period of stress began ('pre-stress'), and then before each day's stress. Residents were bled before stress on the first and thirteenth day. Residents always behaved aggressively towards newcomers. By the end of the stress period, all newcomers were subordinate to residents. In newcomers (n = 8) after 3-4 days of social stress, CBG binding capacity had fallen (P = 0.0025), while free cortisol concentrations had risen (P = 0.0016) from pre-stress values. In contrast, total cortisol did not change. In residents, CBG had decreased slightly but significantly (P = 0.0162) after 12 days of stress. Residents and newcomers did not differ in pre-stress CBG binding capacity, total or free cortisol concentrations. However, by the second week of stress, CBG binding capacity was lower (P = 0.015) and free cortisol higher (P = 0.030) in newcomers (n = 3) than in residents. Total cortisol did not differ between the groups. In conclusion social stress clearly affected the adrenal axis of subordinate newcomer horses, lowering the binding capacity of CBG and raising free cortisol concentrations. However, no effect of stress could be detected when only total cortisol was measured. Therefore, to assess adrenal axis status accurately in horses, it is essential to monitor the binding capacity of CBG and free cortisol concentrations in addition to total cortisol levels.

Effect of Binding to Plasma Proteins on the Interpretation of Plasma Cortisol Concentrations after Accidental Injury

1981 ◽  
Vol 61 (4) ◽  
pp. 399-405 ◽  
Author(s):  
R. N. Barton ◽  
B. J. Passingham
Keyword(s):  
Plasma Proteins ◽  
Plasma Cortisol ◽  
Equilibrium Dialysis ◽  
Cortisol Concentration ◽  
Multiple Equilibrium ◽  
Albumin Concentration ◽  
Trauma Patients ◽  
Accidental Injury ◽  
Total Cortisol ◽  
Free Cortisol

1. The binding of cortisol to plasma proteins has been studied by multiple equilibrium dialysis of plasma samples taken from 14 patients before treatment after moderate or severe accidental injury and 2–5, 6–12 and 14–25 days later. 2. The total plasma cortisol concentration was initially high, but fell by 6–12 days to stable values probably near the upper limit of normal. 3. The plasma albumin and total protein concentrations fell during the first few days after the injury, but the fall in albumin was proportionally the greater. Both were rising again at the end of the study period. The albumin concentration was positively correlated with an index of its binding to cortisol calculable from the dialysis data. 4. The concentration of corticosteroid-binding globulin (CBG) rose between weeks 1 and 2 after trauma, with no statistically significant change before or afterwards. 5. The changes in binding proteins after injury were relatively small and did not greatly alter the relationship between free and total cortisol concentrations in plasma. It is concluded that in most trauma patients changes in free cortisol, generally considered to be the active fraction in plasma, can be followed adequately by measuring the total cortisol concentration.

Seasonal changes in plasma androgens, glucocorticoids and glucocorticoid-binding proteins in the marsupial sugar glider Petaurus breviceps

1992 ◽  
Vol 132 (1) ◽  
pp. 21-31 ◽  
Author(s):  
A. J. Bradley ◽  
D. M. Stoddart
Keyword(s):  
Plasma Concentration ◽  
Breeding Season ◽  
Binding Constant ◽  
Binding Capacity ◽  
Equilibrium Dialysis ◽  
Plasma Testosterone ◽  
High Affinity ◽  
Sugar Glider ◽  
Free Cortisol ◽  
Petaurus Breviceps

ABSTRACT An investigation spanning two breeding seasons was carried out to examine endocrine changes associated with reproduction in a wild population of the marsupial sugar glider Petaurus breviceps, a small arboreal gliding possum. Using techniques of equilibrium dialysis and polyacrylamide gel electrophoresis at steady-state conditions, a high-affinity, low-capacity glucocorticoid-binding protein was demonstrated in the plasma of Petaurus breviceps. Equilibrium dialysis at 36 °C using cortisol gave a high-affinity binding constant of 95 ± 5·2 litres/μmol for a presumed corticosteroid-binding globulin (CBG) while the binding constant for the cortisol-albumin interaction was 3·5 ± 0·4 litres/mmol. There was no difference between the sexes in the affinity of binding of cortisol to CBG; however, the cortisol-binding capacity underwent seasonal variation in both sexes. Progesterone was bound strongly to the presumed CBG while neither oestradiol nor aldosterone appeared to be bound with high affinity to P. breviceps plasma. In the males, peaks in the plasma concentration of testosterone coincided with the July–September breeding season in both years. A significant inverse relationship was shown to exist between the plasma testosterone concentration and the CBG-binding capacity. In both sexes an increase occurred in the plasma concentration of free cortisol during the first breeding season, a pattern which was not repeated in the subsequent breeding season, possibly due to a lower population density in that year. Journal of Endocrinology (1992) 132, 21–31

scholarly journals The effect of manipulating growth in sheep by diet or anabolic agents on plasma cortisol and muscle glucocorticoid receptors

1986 ◽  
Vol 56 (1) ◽  
pp. 289-304 ◽  
Author(s):  
P. M. Sharpe ◽  
P. J. Buttery ◽  
N. B. Haynes
Keyword(s):  
Skeletal Muscle ◽  
Plasma Cortisol ◽  
Glucocorticoid Receptors ◽  
Binding Capacity ◽  
Cortisol Concentration ◽  
The Other ◽  
Trenbolone Acetate ◽  
Relative Binding Affinity ◽  
Relative Binding ◽  
Free Cortisol

1. The cortisol status (total plasma cortisol concentration, free cortisol concentration, transcortin capacity) and the characteristics of skeletal muscle binding for cortisol and dexamethasone were examined in female lambs either implanted with Zeranol or trenbolone acetate or whose dietary intake was restricted.2. The skeletal muscle glucocorticoid receptor had a high affinity for the glucocorticoid triamcinolone (relative binding affinity 0.85) and cortisol (relative binding affinity 0.51) with virtually no affinity for trenbolone.3. Trenbolone acetate treatment reduced the binding capacity of sheep skeletal muscle for cortisol within 2 d of implantation. The other treatments had little effect except a small reduction in the animals where food intake was restricted. Similarly, binding capacity for dexamethasone was reduced by trenbolone acetate treatment but was not affected by the other treatments. This reduction in trenbolone acetate-treated animals is, at least in part, due to a reduction in glucocorticoid receptors.4. Transcortin capacity was elevated by Zeranol treatment but reduced with diet restriction or trenbolone treatment.5. No support for the suggestion of free cortisol concentration being important in the growth-promoting mechanism of trenbolone or Zeranol was obtained.6. Although insulin concentrations were not significantly altered by treatment (P > 0.05), when combining all the animals there was evidence of a negative correlation between total cortiso1: insulin vaue (P < 0.05) or free cortisol: insulin value and growth rate (P < 0.001). Free cortisol was negatively correlated to growth rate (P < 0.05) and transcortin capacity positively correlated (P < 0.01).

Free norethisterone as reflected by saliva concentrations of norethisterone during oral contraceptive use

1981 ◽  
Vol 98 (3) ◽  
pp. 470-476 ◽  
Author(s):  
Viveca Odlind ◽  
Elof D. B. Johansson
Keyword(s):  
Oral Contraceptive ◽  
Contraceptive Use ◽  
Equilibrium Dialysis ◽  
Plasma Concentrations ◽  
Free Fraction ◽  
Sex Hormone Binding Globulin ◽  
Total Plasma ◽  
Healthy Women ◽  
Oral Contraceptive Use ◽  
Epileptic Woman

Abstract. Saliva and plasma concentrations of norethisterone (NET) were determined by a radioimmunoassay in 5 healthy women and in one epileptic woman on phenytoin treatment during a 21-day cycle on an oral contraceptive containing 3 mg NET-acetate and 0.05 mg ethinyloestradiol. Plasma non-protein bound concentrations of NET were determined by equilibrium dialysis. Sex hormone binding globulin (SHBG) was measured in all samples. An excellent correlation was found between plasma total, plasma non-protein bound and saliva levels of NET. Plasma non-protein bound and saliva concentrations were in the same range throughout, indicating that saliva concentrations reflect the free fraction of NET in plasma. SHBG increased considerably in all women. A slight decrease in the ratio between total and non-protein bound concentrations was found with time, possibly reflecting a slight increase in protein binding with increasing SHBG. The woman on anticonvulsant therapy had plasma total, plasma unbound and saliva NET concentrations that were only 30 per cent of those of the healthy women. The relationship between the different fractions was similar to that found in the healthy women. The non-protein bound fraction of NET was 4–5 per cent of the total in all women studied.

scholarly journals Maternal Corticotropin-Releasing Hormone Is Increased with Impending Preterm Birth

1998 ◽  
Vol 83 (5) ◽  
pp. 1585-1591 ◽  
Author(s):  
C. Korebrits ◽  
M. M. Ramirez ◽  
L. Watson ◽  
E. Brinkman ◽  
A. D. Bocking ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Preterm Birth ◽  
Preterm Labor ◽  
Plasma Cortisol ◽  
Binding Capacity ◽  
Normal Subjects ◽  
Maternal Plasma ◽  
Predictive Values ◽  
Free Cortisol ◽  
Threatened Preterm Labor

The objective of this study was to test the hypothesis that maternal CRH concentrations are elevated in women experiencing threatened preterm labor who subsequently give birth within 24 h compared to those in women who do not. We also characterized the changes in maternal plasma cortisol, ACTH, corticosteroid binding capacity (CBC), and CRH concentrations in 28 healthy pregnant women between 20–38 weeks gestation. Overall, maternal plasma CRH concentrations were significantly greater (P &lt; 0.05) in those women giving birth within 24 h (1343.3 ± 143.9 pg/mL; n = 81) compared to those in women who did not (714.5 ± 64.8 pg/mL; n = 144) or those in normal subjects. This difference was present between 28–36 weeks, but not 24–28 weeks gestation. The ratio of maternal cortisol to CBC was also significantly greater (P &lt; 0.05; 0.65 ± 0.04; n = 82) in women giving birth within 24 h than in those who did not (0.55 ± 0.02; n = 136). This difference was significant at all gestational ages studied. Elevated CRH concentrations and bioavailability of free cortisol may both be implicated in the pathogenesis of preterm labor in some women. Further prospective clinical trials are warranted to determine the positive and negative predictive values of maternal CRH concentrations and/or the ratio of cortisol/CBC for identifying women with threatened preterm labor destined to give birth within 24 h.

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