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

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).

1994 ◽  
Vol 58 (3) ◽  
pp. 357-364 ◽  
Author(s):  
H. Gallbraith ◽  
A. D. Berry

AbstractTwenty-five Border Leicester ♂ × Blackface ♀ wether lambs aged about 4 months and weighing on average 28·5 kg were allocated to be treated with the naturally occurring steroid testosterone or trenbolone acetate or nandrolone phenylpropionate which are steroids synthetically produced. Treatment groups were as follows: untreated controls (C); 50 mg testosterone (T); 50 mg trenbolone acetate (TA); 50 mg testosterone + 50 mg trenbolone acetate (TTA) or 50 mg nandrolone phenylpropionate (N). Implants were given at 100 and again at 63 days before slaughter. The lambs were offered to appetite a good quality diet containing, per kg dry matter, an estimated 11·0 MJ metabolizable energy and 185 g crude protein. Comparisons were made for the main effects of T and TA and also interactions between T and TA. Effects due to N were assessed statistically against untreated controls. Treatment with T, on average, increased live-weight gain (LWG), empty body weight (EBW) and reduced backfat thickness and the weight (g/kg EBW) of perirenal and retroperitoneal fat. Main effects due to TA were increases in killing-out ratio and depth of the gigot joint and reductions in backfat thickness. Treatment with N increased the empty body weight and (g/kg) carcass ash. Non-significant (P > 0·05) trends were suggested for increases in carcass crude protein due to T and TA treatments. T and TA but not N treatments exhibited marked androgenic activity in increasing the weight (mg/kg EBW) of the accessary vesicular gland. TA and N, but not T, reduced the weight (g/kg EBW) of the thymus gland.The maximum binding capacity of post-morte m skeletal muscle (m. gluteus) for (3H)-dexamethasone was reduced by TA but increased by T and N. These results suggest differences in the binding capacity of corticosteroid receptors which may be related to differences in the effects of T and TA on protein metabolism in skeletal muscle.


1967 ◽  
Vol 50 (5) ◽  
pp. 1327-1352 ◽  
Author(s):  
Arselio P. Carvalho ◽  
Barbara Leo

Fragmented sarcoplasmic reticulum isolated from skeletal muscle of the rabbit has a cation-binding capacity of about 350 µeq/g of protein at neutral pH. The same binding sites bind Ca, Mg, K, and H ions and, consequently, the selective binding of Ca induced by ATP releases an amount of the other cations equivalent to the Ca taken up. At pH values below 6.2, an increasing number of binding sites are associated with H+, and ATP induces exchange of Ca mostly for H+. At pH values above 6.2, the binding sites exist in the form of Mg and K, and Ca is bound in exchange for these cations. The total bound Ca + Mg + K, expressed in microequivalents of cations bound per gram of protein, is approximately constant at various pCa values, which indicates a stoichiometric exchange of Ca for the other cations. To accomplish the same degree of exchange of Ca for other cations bound, in the absence of ATP, concentrations of free Ca++ of about 1000-fold higher than those needed in the presence of ATP are required in the medium. We cannot distinguish between a mechanism whereby Ca actively transported into a compartment of the microsomal vesicles containing also the binding sites is bound passively to these sites in exchange for Mg, K, and H and another in which ATP selectively increases the affinity of surface-binding sites for Ca. Irrespective of the mechanism of accumulation, the Ca retained does not contribute to the activity of the cation in the membrane fraction. Caffeine (10 mM) has no effect on the binding of Ca, but releases a more labile fraction of Ca, which presumably accumulates in excess of the bound Ca. Procaine (5 mM) antagonizes the effect of caffeine. Acetylcholine and epinephrine have no effect on the binding of Ca.


1998 ◽  
Vol 157 (3) ◽  
pp. 425-432 ◽  
Author(s):  
SL Alexander ◽  
CH Irvine

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.


1981 ◽  
Vol 61 (4) ◽  
pp. 399-405 ◽  
Author(s):  
R. N. Barton ◽  
B. J. Passingham

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.


1986 ◽  
Vol 108 (1) ◽  
pp. 63-68 ◽  
Author(s):  
I. R. McDonald ◽  
A. K. Lee ◽  
K. A. Than ◽  
R. W. Martin

ABSTRACT In an investigation of the factors leading to the increase in the concentration of plasma free glucocorticoid, which results in immunosuppression and death after mating of all males in natural populations of a small shrew-like marsupial, the dusky antechinus (Antechinus swainsonii), the integrity of the glucocorticoid feedback control of the concentration of plasma cortisol was examined by use of dexamethasone-suppression tests. Injection of 0·2 mg dexamethasone/kg i.m. caused a marked fall in the concentration of plasma cortisol 17 h later, approximately 2 months and 2 weeks before the annual mating period in mid-July. However, the same dose had no significant effect on the increased concentration of plasma cortisol characteristic of the mid- to late July mating period. Injection of 100 i.u. ACTH/kg i.m. caused a significant increase in the concentration of plasma cortisol 6–7 h later on all occasions, indicating that the responsiveness of the adrenal cortex to ACTH did not change. Pretreatment with dexamethasone had no effect on the ACTH-stimulated cortisol concentration, ruling out a possible direct effect of dexamethasone on adrenocortical secretion in this species. Dexamethasone also reduced the concentration of plasma testosterone when the level was low, before the mating period, but not when the level was high, at the beginning of the mating period. It is concluded that, in association with a rapid increase in the concentration of plasma testosterone, an increase in aggression and intense mating activity, glucocorticoid feedback control of ACTH secretion is impaired. This contributes to the rapid and sustained rise in the concentration of plasma free cortisol to immunosuppressive levels. J. Endocr. (1986) 108, 63–68


2000 ◽  
Vol 165 (2) ◽  
pp. 527-532 ◽  
Author(s):  
N Picard-Hagen ◽  
V Gayrard ◽  
M Alvinerie ◽  
V Laroute ◽  
C Touron ◽  
...  

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.


1998 ◽  
Vol 83 (5) ◽  
pp. 1585-1591 ◽  
Author(s):  
C. Korebrits ◽  
M. M. Ramirez ◽  
L. Watson ◽  
E. Brinkman ◽  
A. D. Bocking ◽  
...  

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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