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.

Concentrations, metabolic clearance rates, production rates and plasma binding of cortisol in Antarctic phocid seals

1993 ◽  
Vol 129 (4) ◽  
pp. 356-359 ◽  
Author(s):  
Graham C Liggins ◽  
John T France ◽  
Robert C Schneider ◽  
Bruce S Knox ◽  
Warren M Zapol
Keyword(s):  
Binding Capacity ◽  
Plasma Concentrations ◽  
Human Values ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Production Rates ◽  
High Production Rate ◽  
Free Cortisol ◽  
Phocid Seals ◽  
Cortisol Levels

We have reported previously that plasma of the Weddell seal, a member of the phocid family, contains a very high concentration of cortisol. The present study was undertaken to determine whether high cortisol levels were common to seals in the Antarctic environment, or to other phocidae, and to determine the mechanism of the hypercortisolaemia. High levels of cortisol (0.82–2.38 μmol/l) were found in 4 phocidae (Weddell, crabeater, leopard and Southern elephant seals), whereas levels in a member of the otariid family (Antarctic fur seal) were similar to human values. Metabolic clearance rates (MCR) and production rates (PR) of cortisol were determined in the field in Weddell (N = 1), crabeater (N= 3) and leopard (N= 3) seals following bolus injections of [3H] cortisol. The MCR and PR did not differ between the three phocids, but whereas the MCR of 410–590 1/day was twice that of human values, the PR of 460–1180 μmol·m−2·d−1 was up to 40-fold greater. The binding capacity of corticosteroid-binding globulin (CBG) was equal to or greater than the plasma concentrations of cortisol, resulting in relatively low concentrations of free cortisol. We conclude that hypercortisolaemia is maintained in phocid seals mainly by a high production rate—the highest (corrected for surface area) reported in any species. The relatively low cortisol levels in otariid seals studied in the same environment suggest that the high PR in phocidae is unrelated to the harsh climatic conditions, but may be part of their adaptation for diving to extreme depths. The phocid seals and New World primates have similarly high levels of cortisol and a high PR but CBG in the primates has low binding capacity and affinity and cortisol is mainly free.

scholarly journals Novel Corticosteroid-Binding Globulin Variant That Lacks Steroid Binding Activity

2010 ◽  
Vol 31 (4) ◽  
pp. 607-608
Author(s):  
I. Perogamvros ◽  
C. Underhill ◽  
D. E. Henley ◽  
K. D. Hadfield ◽  
W. G. Newman ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Serum Cortisol ◽  
Pulse Frequency ◽  
Binding Activity ◽  
Glucocorticoid Signaling ◽  
Free Cortisol ◽  
Corticosteroid Binding Globulin ◽  
Undetectable Serum ◽  
Steroid Binding ◽  
Cortisol Levels

Abstract Background: Corticosteroid-binding globulin (CBG) is the principal carrier for glucocorticoids in the circulation and a regulator of their bioavailability. Inherited CBG deficiencies are rarely reported, and only three causative mutations in four families have been described. Patients, Methods, and Results: In a 26-yr-old female with hypotension, fatigue, and undetectable serum cortisol at presentation, we have identified a novel homozygous c.776g>t transversion in exon 3 of the CBG (SERPINA6) gene. This results in a p.Gly237Val substitution that is predicted to influence the positioning of two β-sheets that constitute part of the CBG steroid-binding site. Two siblings were also homozygous for the variant, whereas her mother and an unaffected sibling were heterozygous. No other symptomatic family members were identified apart from the proband. Individuals homozygous for the variant had serum CBG levels below the reference range when measured by RIA, but CBG was unmeasurable in cortisol-binding capacity assays. In the same individuals, we observed very low baseline and stimulated serum cortisol levels but normal free serum and salivary cortisol and plasma ACTH. In a study of ultradian cortisol pulsatility, increased pulse frequency was only observed in the proband. Conclusion: We describe a novel CBG variant that lacks steroid binding. All mutant homozygotes have very low serum cortisol, but normal free cortisol levels. The only biochemical feature to distinguish the symptomatic subject was increased cortisol pulsatility, and we suggest that this may influence glucocorticoid signaling and contribute to symptoms previously associated with CBG deficiency.

scholarly journals Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study

2009 ◽  
Vol 161 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Gudmundur Johannsson ◽  
Ragnhildur Bergthorsdottir ◽  
Anna G Nilsson ◽  
Hans Lennernas ◽  
Thomas Hedner ◽  
...  
Keyword(s):  
Single Dose ◽  
Replacement Therapy ◽  
Plasma Cortisol ◽  
Plasma Concentrations ◽  
Pharmacokinetic Studies ◽  
Double Blind ◽  
Once Daily ◽  
Physiological Serum ◽  
Cortisol Levels ◽  
Dual Release

BackgroundEndogenous plasma cortisol levels have a well-defined circadian rhythm. The aim of this project is to develop a once daily oral dual-release formulation for cortisol replacement therapy that mimics the diurnal variation in the plasma cortisol profile.ObjectiveTo determine single-dose plasma pharmacokinetics and dose-proportionality of oral 5 and 20 mg dual-release hydrocortisone tablets in healthy volunteers. In addition, the effect of food intake was investigated for the 20 mg dose.DesignA randomised, controlled, two-way cross-over, double-blind, phase I study of oral hydrocortisone (modified (dual) release; 5 and 20 mg) with an open food-interaction arm.MethodsThe single dose pharmacokinetic studies were performed with betamethasone suppression. The two first study days were blinded and randomised between morning administration of 5 and 20 mg tablet in a fasting state. The third day was open with a 20 mg tablet taken 30 min after a high-calorie, high-fat meal. The plasma samples were assayed using both a validated LC–MS/MS and an immunoassay. The plasma pharmacokinetic variables were calculated using non-compartmental data analysis.ResultsThe time to reach a clinically significant plasma concentration of cortisol (>200 nmol/l) was within 20 min and a mean peak of 431 (s.d. 126) nmol/l was obtained within 50 min after administration of the 20 mg tablet. Plasma cortisol levels remained above 200 nmol/l for around 6 h thereafter and all plasma concentrations 18–24 h after intake were below 50 nmol/l. In the fed state the time to reach 200 nmol/l was delayed by 28 and 9 min based on LC–MS/MS and immunoassay, respectively. The 5 and 20 mg tablets produced an increase in plasma exposure of cortisol that was not fully dose proportional.ConclusionThe dual release hydrocortisone tablet with once-daily administration produced a diurnal plasma cortisol profile mimicking the physiological serum cortisol profile.

scholarly journals Responses of New World flying squirrels to the acute stress of capture and handling

2015 ◽  
Vol 97 (1) ◽  
pp. 80-88 ◽  
Author(s):  
Lanna M. Desantis ◽  
Jeff Bowman ◽  
Candace V. Lahoda ◽  
Rudy Boonstra ◽  
Gary Burness
Keyword(s):  
Stress Response ◽  
New World ◽  
Binding Capacity ◽  
Biologically Active ◽  
Stress Axis ◽  
Neutrophil Lymphocyte Ratio ◽  
Flying Squirrels ◽  
Physiological Variables ◽  
Total Cortisol ◽  
Cortisol Levels

Abstract Northern ( Glaucomys sabrinus ) and southern ( G. volans ) flying squirrels have glucocorticoid (GC; stress hormone) levels higher than most vertebrates but virtually no binding capacity for these GCs via the carrier protein, corticosteroid-binding globulin. Thus, their total GCs are essentially all free and biologically active. However, the GC estimates come from blood samples taken after squirrels had been in live traps, and thus in a stress-induced state. Obtaining baseline values for physiological variables is valuable for assessing the response of vertebrates to stressors in their environment. We compared baseline plasma total cortisol levels (within 3min of capture) to stress-induced levels (after 30min of trap restraint) in both flying squirrel species. We recorded baseline cortisol levels that were some of the highest ever reported for mammals, indicating their stress axes operate at a higher set point than most other species. As part of the stress response, we also measured 4 indices in addition to cortisol. Total cortisol and free fatty acids increased in both species, as predicted. In contrast with our predictions, blood glucose and neutrophil/lymphocyte ratio showed no overall change, and hematocrit decreased significantly. New World flying squirrels therefore appear to have a stress response that differs from many other mammals. The selective forces driving the physiology of these animals remain elusive, but this lineage may provide an interesting comparative system for the study of stress axis function and its evolution among vertebrates.

Corticosteroid-binding globulin levels in North American sciurids: implications for the flying squirrel stress axis

2018 ◽  
Vol 96 (10) ◽  
pp. 1090-1096 ◽  
Author(s):  
Lanna M. Desantis ◽  
Jeff Bowman ◽  
Erin Faught ◽  
Rudy Boonstra ◽  
Mathilakath M. Vijayan ◽  
...  
Keyword(s):  
New World ◽  
Stress Axis ◽  
Glaucomys Sabrinus ◽  
Evolutionary Time ◽  
Glaucomys Volans ◽  
Flying Squirrels ◽  
Total Cortisol ◽  
Corticosteroid Binding Globulin ◽  
Tree Squirrels ◽  
Cortisol Levels

Corticosteroid-binding globulin (CBG) helps to regulate tissue bioavailability of circulating glucocorticoids (GCs), and in most vertebrates, ≥80%–90% of GCs bind to this protein. New World flying squirrels have higher plasma total cortisol levels (the primary corticosteroid in sciurids) than most vertebrates. Recent research suggests that flying squirrels have either low amounts of CBG or CBG molecules that have a low binding affinity for cortisol, as this taxon appears to exhibit very low proportions of cortisol bound to CBG. To test whether CBG levels have been adjusted over evolutionary time, we assessed the levels of this protein in the plasma of northern (Glaucomys sabrinus (Shaw, 1801)) and southern (Glaucomys volans (Linnaeus, 1758)) flying squirrels using immunoblotting, and compared the relative levels among three phylogenetically related species of sciurids. We also compared the pattern of CBG levels with cortisol levels for the same individuals. Flying squirrels had higher cortisol levels than the other species, but similar levels of CBG to their closest relatives (tree squirrels). We conclude that CBG levels in flying squirrels have not been adjusted over evolutionary time, and thus, the uncoupling of CBG levels from cortisol concentrations may represent an evolutionary modification in the lineage leading to New World flying squirrels.

THE PLASMA CONCENTRATIONS OF FREE AND PROTEIN-BOUND CORTISOL IN HYPOPROTEINAEMIA

1966 ◽  
Vol 34 (2) ◽  
pp. 265-270 ◽  
Author(s):  
P. J. LEONARD ◽  
P. G. D'ARBELA
Keyword(s):  
Plasma Level ◽  
Cortisol Level ◽  
Plasma Concentrations ◽  
Biochemical Changes ◽  
Striking Similarity ◽  
Control Group ◽  
Absolute Level ◽  
Total Cortisol ◽  
Control Subjects ◽  
Free Cortisol

SUMMARY The plasma level and percentage of bound cortisol were measured in sixteen African subjects with hypoproteinaemia of varying aetiologies. When compared with a control group it was found that the percentage of the steroid bound was significantly reduced but that the total cortisol level did not differ from that found in the control subjects. This resulted in a significant increase in the absolute level of free cortisol in the hypoproteinaemic subjects. Attention is drawn to the striking similarity between many of the physical and biochemical changes seen in kwashiorkor and those found in Cushing's syndrome.

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.

DIFFERENCES IN CONCENTRATIONS OF PLASMA CORTISOL IN THE TROUT AND THE EEL FOLLOWING ADAPTATION TO BLACK OR WHITE BACKGROUNDS

1981 ◽  
Vol 89 (1) ◽  
pp. 135-140 ◽  
Author(s):  
BRIDGET I. BAKER ◽  
THERESA A. RANCE
Keyword(s):  
Rainbow Trout ◽  
Plasma Cortisol ◽  
Binding Capacity ◽  
Anguilla Anguilla ◽  
Short Photoperiod ◽  
Salmo Gairdneri ◽  
Pars Intermedia ◽  
Total Cortisol ◽  
The Difference ◽  
Long Photoperiod

When rainbow trout (Salmo gairdneri) and eels (Anguilla anguilla) were kept in black tanks for 3—4 weeks, their plasma cortisol titres were about fourfold higher than in fish kept in white tanks. In trout, the difference was apparent only under a long photoperiod of 16 h light: 8 h darkness, but in eels the difference was clear under both a long or short photoperiod (9·5 h light: 14·5 h darkness). It is suggested that the increase in plasma cortisol seen in black-adapted fish is dependent on either ACTH or MSH secreted by the pars intermedia melanotrophs. No difference was seen either in the total cortisol-binding capacity of the plasma nor in interrenal histology in trout from black or white backgrounds.

Adrenal function in lambs treated with androgenic and oestrogenic growth stimulants

1987 ◽  
Vol 44 (2) ◽  
pp. 241-249 ◽  
Author(s):  
M. N. Sillence ◽  
K. M. Thomas ◽  
H. Anil ◽  
E. J. Redfern ◽  
R. G. Rodway
Keyword(s):  
Plasma Cortisol ◽  
Plasma Insulin ◽  
Anabolic Steroids ◽  
Free Form ◽  
Oestrogen Treatment ◽  
Growth Measurement ◽  
Acth Challenge ◽  
The Third ◽  
Free Cortisol ◽  
Cortisol Levels

ABSTRACTThree experiments were carried out in which plasma cortisol concentrations were measured hourly in lambs treated with various anabolic steroids. In the first experiment, female lambs were implanted with trenbolone acetate (TBA) and plasma cortisol was measured for 24-h periods 4 weeks after implantation and 1 week after reimplantation. Plasma cortisol levels were unaltered 4 weeks after treatment, but were found to be significantly lower 1 week after retreatment. On this occasion, peak concentrations of cortisol after ACTH challenge were also reduced by TBA. In the second experiment, female lambs were implanted with a mixture of TBA and oestradiol and plasma cortisol measured 1 and 4 weeks later. Results were similar to the first experiment although the reduction in plasma cortisol was less. In the third experiment, castrated male lambs were implanted with either TBA, TBA plus oestradiol or a long-acting oestradiol implant. In this experiment, only oestradiol affected plasma cortisol levels, causing a large elevation. All three treatments stimulated growth. Measurement of bound and free cortisol concentration in the third experiment indicated that oestradiol treatment tended to increase the proportion of cortisol present in the free form.These results suggest that an inhibition of cortisol secretion may be important in the anabolic response of female sheep to TBA. In the male, however, cortisol concentrations are naturally lower and are not further reduced by TBA treatment.Plasma insulin concentrations were also measured in the castrated males. Neither TBA nor the combined implant altered insulin levels, but oestrogen treatment resulted in a small increase in insulin. The diurnal pattern of plasma insulin closely paralleled that of cortisol.

MEASUREMENT OF PLASMA CORTISOL LEVELS IN THE EEL ANGUILLA ANGUILLA IN RELATION TO OSMOTIC ADJUSTMENTS

1971 ◽  
Vol 50 (1) ◽  
pp. 75-96 ◽  
Author(s):  
J. N. BALL ◽  
I. CHESTER JONES ◽  
M. E. FORSTER ◽  
G. HARGREAVES ◽  
E. F. HAWKINS ◽  
...  
Keyword(s):  
Plasma Cortisol ◽  
Sea Water ◽  
Anguilla Anguilla ◽  
Plasma Cortisol Level ◽  
Hormonal Control ◽  
Total Cortisol ◽  
Competitive Protein Binding ◽  
Low Levels ◽  
Cortisol Levels

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.

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