Sire breed of calf influences peripartum endocrine profiles and postpartum anestrus in Brahman cows

The literature indicates that sire breed of calf influences beef calf performance. However, there is little information concerning sire breed of calf effects on reproduction in beef cows. In this experiment, Angus (A), Brahman (B), or Tuli (T) bulls were bred to 136 Brahman (B) cows to examine sire breed of calf influence on peripartum hormone profiles and the length of postpartum anestrus. Cows were bled from 7 d prepartum to 28 d postpartum to determine peripartum hormone concentrations. Cows carrying AB calves had greater (P < 0.05) prepartum estradiol-17 beta concentrations than did cows carrying BB and TB calves. Prepartum and postpartum progesterone concentrations did not differ between cows with AB, BB, and TB calves. Cows with TB calves had lower (P < 0.01) 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) concentrations than did cows with AB and BB calves during the early postpartum period. Adjusting for birth weight removed the sire breed of calf effect on postpartum PGFM concentrations, but not prepartum estradiol-17 beta. Postpartum anestrus was shorter (P < 0.05) for cows nursing BB calves (84 +/- 6 d) than for cows nursing AB (101 +/- 6 d) or TB calves (110 +/- 7 d). Adjustment for estradiol or PGFM concentrations did not reduce sire breed of calf effects on the length of postpartum anestrus. Further work is heeded to determine how calf genotype may modulate the postpartum reproductive function of the dam.     

Genotypic effects on norepinephrine-induced changes in thermogenesis, metabolic hormones, and metabolites in newborn calves

Heat production was measured in newborn Angus-, Brahman-, and Tuli-sired calves born to Angus (n = 20) and Brahman (n = 26) dams, before (thermoneutral metabolic rate, TMR) and after norepinephrine (NE) infusion (peak metabolic rate, PMR), to assess genotypic effects on nonshivering thermogenesis in brown adipose tissue. Calves were fed pooled colostrum, fitted with jugular catheters, and placed in a temperature-controlled (37 degrees C) water immersion system. Heat production, determined by indirect calorimetry, and tympanic temperature were measured continuously in calves from approximately 3 to 6 h of age. Blood samples were collected at birth and at 0, 5, 20, 40, 60, 80, 100, and 120 min relative to NE infusion (35 micrograms.min-1.kg BW-1 for 4 min), and plasma was analyzed for metabolites (glucose, NEFA, and urea nitrogen [PUN]) and hormones (cortisol, triiodothyronine [T3] and thyroxine [T4]). Weight-specific TMR (cal.min-1.kg-1) was not affected by breed of sire or dam, although weight-specific PMR (cal.min-1.kg-1) was lower (P < .01) in Brahman-sired calves than in Angus- or Tuli-sired calves and was lower (P < .001) in calves born to Brahman rather than Angus dams. The reduction in weight-specific PMR due to the maternal Brahman influence was sire-breed dependent, and the reduction was largest (P < .01) for Tuli-sired (34.3%), intermediate (P < .05) for Brahman-sired (15.1%), and lowest (P > .25) for Angus-sired calves (4.1%). The PMR:TMR ratio was 1.80 and 2.21 +/- .06 in calves born to Brahman and Angus dams, respectively. Peak tympanic temperature was .6 degree C lower (P < .01) in calves born to Brahman rather than Angus dams. At birth, plasma NEFA concentrations were higher (P < .001) and glucose tended (P = .13) to be higher in calves born to Brahman rather than Angus dams. Cortisol, T3, and T4 concentrations at birth were higher in calves born to Brahman dams than in those born to Angus dams. These results suggest that calves born to Brahman dams may have less thermogenically active brown adipose tissue than calves born to Angus dams, which may contribute to the relative cold intolerance of calves with Bos indicus inheritance.     

Comparisons among Tuli-, Brahman-, and Angus-sired heifers: intake, digesta kinetics, and grazing behavior

As part of an evaluation of Tuli crossbred cattle, forage intake, digesta kinetics, and grazing behavior were estimated in two Texas environments. In humid east Texas, Tuli x Brahman heifers were compared with purebred Angus and Brahman and Angus x Brahman heifers. Fecal output, forage intake, compartmental mass, and compartmental residence time did not differ among breeds. Angus and Brahman heifers had different (P < . 02) gastrointestinal residence times (51.1+/-1.56 vs 43.1+/-1.56 h, respectively), but values for the purebreds did not differ from those for Tuli x Brahman or Angus x Brahman heifers. Angus heifers had shorter (P < .05) 24-h grazing times (398+/-15.4 min/d) and fewer (P < .05) grazing periods (7+/-.4) than Tuli x Brahman (552+/-16.8 min/d and 10+/-.4), Angus x Brahman (507+/-18.4 min/d and 9+/-.5), and Brahman (560-/+ 16.8 min/d and 9+/-.4, respectively) heifers. In semiarid southwest Texas, Tuli x Angus heifers were compared with purebred Angus and Brahman and Brahman x Angus heifers. Fecal output and forage intake were similar in Tuli x Angus and Brahman x Angus heifers (14.2+/-.69 and 14.9+/-.91 g fecal DM/ [d.kg BW] and 24.5+/-1.33 and 25.6+/-1.75 g/d of forage DMI, respectively) but higher (P < .05) than those of purebred Brahman heifers (12.2+/-.64 and 20.3+/-1.23 g/[d.kg BW] of fecal DM and forage DMI, respectively). Grazing times did not differ among breeds. We conclude that Tuli-sired heifers are likely to be as productive as Brahman crossbred heifers in Texas, based on the similarities in intake, digesta dynamics, and grazing behavior.     

Reproductive performance of cows mated to and preweaning performance of calves sired by Brahman vs alternative subtropically adapted breeds

Comparisons involving Brahman and Brahman-derivative (Brangus, Santa Gertrudis, Beef-master, Simbrah, Braford) sires indicate the following: 1) cows mated to Brangus and Santa Gertrudis bulls had a shorter gestation length than cows mated to Brahman bulls, 2) calves sired by Brangus and Beefmaster bulls were lighter at birth and weaning than calves sired by Brahman bulls, and 3) birth and weaning weights were similar for calves sired by Santa Gertrudis and Brahman bulls and for calves sired by Simbrah and Brahman bulls. Comparisons involving Brahman and other Zebu (Sahiwal, Nellore, Gir, Indu-Brazil, Boran, Romana Red) sires indicate that gestation length was slightly longer for cows mated to Sahiwal and Nellore bulls and that, relative to the Brahman, birth and weaning weights were similar to or lighter for calves sired by bulls of the other Zebu breeds. The only exception to this pattern was birth weight of Indu-Brazil-sired calves, which were heavier than calves sired by Brahman bulls. Comparisons involving Brahman and non-Zebu subtropically adapted (Tuli, Senepol) sires indicate that cows mated to Tuli bulls had a slightly shorter gestation length than cows mated to Brahman bulls and that birth and weaning weights of calves sired by Tuli and Senepol bulls were lighter than those of calves sired by Brahman bulls.     

Medication use patterns among demented, cognitively impaired and cognitively intact community-dwelling elderly people

OBJECTIVE: The present study was conducted in order to describe human hypothalamo-pituitary adrenal (HPA) axis adaptation in a model of repeated physical stress (endurance training) that causes a moderate increase in cortisol levels. SUBJECTS: We performed the same stimulation tests (adrenal stimulation with ACTH or pituitary stimulation with combined CRH/LVP) in a population of 8 endurance-trained athletes in two distinct situations: resting (baseline cortisol values) and 2 h after the end of strenuous exercise (increased cortisol values) to evaluate the HPA axis sensitivity to endogenous sustained increases in cortisol concentrations. MEASUREMENTS: During these tests, saliva and plasma cortisol (Fs and Fp, respectively) were assessed and compared. RESULT: Cortisol values in both plasma and saliva at the end of 2 h of exercise were significantly higher than in rested controls: Fs 11.5 +/- 1.3 vs 6.5 +/- 0.8 nmol.l-1 and Fp 428 +/- 36 vs 279 +/- 27 nmol.l-1 (post exercise vs post rest sessions, respectively, P < 0.001 for both). After either hormone test (CRH/LVP or ACTH), cortisol levels in plasma and saliva increased similarly when rest was compared to post exercise. Saliva variations (delta %) under exogenous hormone stimulation were dramatically greater than plasma variations. For example, under ACTH stimulation, the relative increments in cortisol were on control day: delta Fs 980 +/- 139 vs delta Fp 218 +/- 43% (saliva vs plasma, respectively, P < 0.05) and on exercise day: delta Fs 605 +/- 89 vs delta Fp 102 +/- 14% (saliva vs plasma, respectively, P < 0.05). CONCLUSIONS: In endurance-trained athletes, displaying a moderate but sustained endogenous cortisol increase: (1) ACTH responses following pituitary stimulation are not blunted, (2) cortisol responses following maximal adrenal stimulation are not blunted. Our results favour the hypothesis of a decreased pituitary sensitivity to cortisol negative feedback whereas the hypothesis of a major decreased adrenal sensitivity to ACTH was discarded. The greater ability of saliva assays to detect a cortisol increase strongly supports its use in the study of HPA physiology, whether under basal or dynamic conditions.     

Reproductive performance, calf growth, and milk production of first-calf heifers sired by seven breeds and raised on different levels of nutrition

We evaluated heifers crossbred from seven breeds of sires (Hereford, Angus, Belgian Blue, Piedmontese, Brahman, Boran, and Tuli) and three breeds of dams (Angus, Hereford, and MARC III [four-breed composite]). Heifers were mated to Red Poll sires to calve at 2 yr of age. Heifers were placed in two treatments from weaning to breeding and raised on a high nutrition level (15.8 Mcal ME/d) or on 80% of the high nutrition level (12.6 Mcal ME/d). Breeds differed in the age of the heifers at parturition (P = .03). Birth weights of calves differed by maternal grandsire (P < .001) but not by heifer treatment (P = .91) or maternal grandam (P = .19). Heifers differed in their postpartum interval to estrus by sire breed (P = .001). Calf age at weaning (P = .02), calf ADG (P < .001), and 205-d weight (P < .001) differed between breeds of maternal grandsires. Milk production from 50 to 200 d of lactation was greatest for heifers of Belgian Blue (1,070 +/- 30 kg) and Brahman (1,029 +/- 38 kg) sires. Milk production did not differ with treatment group (P = .84). This study suggests that over a diverse group of breeds, accelerated rates of gain during the postweaning period within the ranges of this study do not result in increased production efficiency of the cows.     

Changes in oxytocin and cortisol levels in primiparous cows after changing from 21 days of suckling calves to machine milking

Four first-calvers of the Black-Pied breed with calves sucking their milk until day 21 of lactation were included in a trial. One suckler cow had four calves. The trial took place within five days which included days 20 and 21 in the first-calvers, that means the last two days with sucking calves (designated as day 1 and day 2 of trial-first and second calf sucking) and days 22 and 24, that means the first and third day after the cows were moved to a cowshed (designated as the third and fifth day of trial-first and third evening machine milking). The first-calvers were separated from the calves and moved to a cowshed at 8 o'clock a.m. on day 3 of trial (Tab. I). The responses to calf sucking were investigated after four-hour prevention of calves to approach the cows (12.00-16.00 p.m.). Blood was sampled with a catheter which was introduced into the vena jugularis a day before the trial outset. Blood samples for cortisol determination were taken in two-hour intervals (when the cows were moved to the cowshed twice in half-an-hour interval and once in an hour interval). Blood samplings were effectuated by day, before, during and after milking, or sucking. Machine milking was finished within 7 to 8 minutes. Two to four calves were intensively sucking a cow within the first 15 minutes, then sucking was irregular. Plasma samples were deep-frozen and stored at -20 degrees C until determinations were performed. Oxytocin and cortisol in the blood plasma were determined by radioassays. In the first evening machine milking (day 3) the second cow yielded 8.23 kg milk while on day 5 in the third milking it was 7.98 kg. The other first-calvers gave by 30-45% less milk on day 3 in comparison with evening milking on day 5 (Tab. II). A trend of the higher average values of oxytocin was observed in machine milking on day 5 of trial if compared with the values recorded during calf sucking, or the first milking (day 3), Fig. 1a, Tab. III. The mean oxytocin concentration during 7-minute milking (12.39 +/- 5.81 pg/ml) was significantly lower in the first-calvers on day 3 in comparison with the mean values recorded on day 5 (28.01 +/- 18.56 pg/ml; P < 0.001), or during sucking (18.32 +/- 7.15 pg/ml; P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)     

Morphologic and cytochemical characteristics of blood cells from Hawaiian green turtles

Previous studies have shown that hypoglycemia may reduce counterregulatory responses to subsequent hypoglycemia in healthy subjects and in patients with diabetes. The effect of hypoglycemia on the hormonal response to a nonhypoglycemic stimulus is uncertain. To test the hypothesis that the cortisol response to corticotropin (ACTH) infusion is independent of antecedent hypoglycemia, 10 healthy subjects received a standard ACTH infusion (0.25 mg Cosyntropin [Organon, West Orange, NJ] intravenously over 240 minutes) at 8:00 AM on day 1 and day 3 and a hypoglycemic insulin clamp study (1 mU/kg/min) at 8:00 AM on day 2. During the hypoglycemic clamp, plasma glucose decreased from 5.0 mmol/L to 2.8 mmol/L for two periods of 120 minutes (mean glucose, 2.9 +/- 0.03 and 2.8 +/- 0.02 mmol/L, respectively) separated by a 60-minute interval of euglycemia (mean glucose, 4.7 +/- 0.01 mmol/L). Seven subjects also had paired control studies in random order during which a 330-minute euglycemic clamp (mean glucose, 5.0 +/- 0.11 mmol/L) instead of a hypoglycemic clamp was performed on day 2. Basal ACTH (4.6 +/- 0.7 v 2.6 +/- 0.4 pmol/L, P < .02) and basal cortisol (435 +/- 46 v 317 +/- 40 nmol/L, P < .02) both decreased from day 1 to day 3 following intervening hypoglycemia. In contrast, with intervening euglycemia, neither basal ACTH (5.9 +/- 1.5 v 4.5 +/- 1.0 pmol/L) nor basal cortisol (340 +/- 38 v 318 +/- 60 nmol/L) were reduced significantly on day 3 compared with day 1. Following interval hypoglycemia, the area under the curve (AUC) for the cortisol response to successive ACTH infusions was increased (4,734 +/- 428 nmol/L over 240 minutes [day 3] v 3,526 +/- 434 nmol/L over 240 minutes [day 1], P < .01). The maximum incremental cortisol response was also significantly increased (805 +/- 63 nmol/L (day 3) v 583 +/- 58 nmol/L (day 1), P < .05). In contrast, the AUC for the cortisol response to successive ACTH infusions with interval euglycemia (3,402 +/- 345 nmol/L over 240 minutes [day 3] v 3,709 +/- 391 nmol/L over 240 minutes [day 1] and the incremental cortisol response (702 +/- 62 nmol/L [day 3] v 592 +/- 85 nmol/L [day 1] were unchanged. Following exposure to intermittent hypoglycemia in healthy humans, fasting morning ACTH and cortisol levels are reduced and the incremental cortisol response to an infusion of ACTH is enhanced. The enhanced cortisol response to exogenous ACTH infusion after intervening hypoglycemia (but not intervening euglycemia) may reflect priming of the adrenal gland by endogenous ACTH produced during the hypoglycemia. These data suggest that adrenal function testing by exogenous ACTH administration is not impaired by prior exposure to hypoglycemia. Moreover, the reduced cortisol response to recurrent hypoglycemia in patients with well-controlled diabetes is not likely the result of impaired adrenal responsiveness.     

Effect of energy source and escape protein on receiving and finishing performance and health of calves

Two receiving and two finishing trials evaluated energy source and escape protein supplementation for calves. In receiving Trial 1, 398 calves (257 +/- 24 kg BW) were used in a 2 x 2 factorial arrangement of treatments. Energy sources were dry-rolled corn (DRC) and wet corn gluten feed (WCGF); each was fed without or with supplemental escape protein (EP). Calves fed WCGF gained slower (P < .05) and consumed less DM (P < .01) than calves fed DRC. Feed efficiency improved (P < .10) with EP supplementation. In finishing Trial 1, 240 calves (305 +/- 21 kg BW) were used. The arrangement of treatments was the same as in receiving Trial 1. Calves fed DRC/WCGF tended (P = .15) to be more efficient and consumed less DM (P < .05) than calves fed DRC. In receiving Trial 2, 315 calves (252 +/- 23 kg BW) were fed diets similar to those fed in receiving Trial 1. Calves fed WCGF consumed less DM (P < .01), gained similarly (P > .15), and were more efficient (P < .10) than calves fed DRC. In finishing Trial 2, 320 calves (298 +/- 23 kg BW) were fed diets containing DRC, DRC/WCGF, high-moisture corn (HMC), HMC/WCGF, and DRC/HMC; each was fed without or with supplemental EP. An energy source x protein supplement interaction was detected for gain (P < .05) and efficiency (P < .01). Results suggest that WCGF has a NEg greater than DRC in receiving diets and a NEg similar to that of DRC but lower than that of HMC in finishing diets.     

Treatment with growth hormone suppresses cortisol production in man

The effect of biosynthetic human growth hormone (GH) on the cortisol production rate was determined in healthy men (N=8) using the stable isotope dilution technique and mass spectrometry. 1alpha,2alpha-D-Cortisol was infused at a dose of 110+/-9 microg/h for 10 hours (8 AM to 6 PM). Blood samples obtained at 20-minute intervals from 2 PM to 6 PM were pooled during two 2-hour periods. Subsequently, each subject received a daily dose of biosynthetic human GH (4 IU/d subcutaneously [SC]) for 7 days. This resulted in an increase of plasma somatomedin C from a basal level of 0.65+/-0.13 U/mL to 1.18+/-1.2 U/mL on day 7 (P < .0001). Plasma concentrations of corticotropin (ACTH) and cortisol-binding globulin (CBG) were similar before and after administration of GH. Determination of the cortisol production rate was repeated on day 7 of treatment with GH. Due to its physiological diurnal rhythmicity, endogenous production of cortisol during basal conditions was higher (P < .05) between 2 and 4 PM (0.70+/-0.30 mg/h) versus 4 to 6 PM (0.55+/-0.28 mg/h). Following treatment with GH, the values were 0.40+/-0.11 mg/h (2 to 4 PM, P < .01 v day 1) and 0.31+/-0.11 mg/h (4 to 6 PM, P < .01 v day 1). Thus, in healthy men, treatment with SC, GH induces a decrease in endogenous cortisol production rates.     

Adrenal responses of Angus x Hereford cattle to the stress of weaning

To test adrenal responsiveness of beef cattle to stress, plasma norepinephrine, epinephrine, and cortisol responses of Angus x Hereford cattle to weaning were measured in blood samples taken from 1) eight cows and their 4- to 6-mo-old calves before and after separation and, the following day, before and after being reunited and 2) an equal number of control animals. After separation and before they were reunited, dams were returned to their original pen and calves to an adjacent pen. Experimental trials were conducted every 2 wk and included two cow/calf pairs per trial. Norepinephrine concentrations tended to increase in calves after separation, were increased (+82 pg/mL, P < .01) on the 2nd d before animals were reunited, and decreased (-88 pg/mL, P < .01) after animals were reunited. Epinephrine concentrations tended to increase in calves after separation, were increased in calves (+128 pg/mL, P < .001) and dams (+104 pg/mL, P < .001) on the 2nd d before animals were reunited, and decreased after calves (-162 pg/mL, P < .001) and dams (-101 pg/ml, P < .001) were reunited. There were no significant effects of time on catecholamine concentrations for control animals. Cortisol concentrations for treated and control animals tended to increase in sequential samples each day; however, the increases were small (approximately 1 ng/mL) and concentrations remained low (> 5 ng/mL). In conclusion, peripheral catecholamine concentrations in beef calves and epinephrine concentrations in dams increased in response to stress associated with weaning and separation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol before and after weight loss

Little is known about the effects of intentional weight loss on the function of the hypothalamic-pituitary-adrenal (HPA) axis of obese individuals. We studied the HPA axis of 34 healthy obese women (body mass index, 40.2 +/- 7.9 kg/m2) before and after a 21.0 +/- 7.9-kg weight loss induced by a 26-week weight loss program that included 12 weeks of a 3350 kJ/day (800 Cal/day) liquid formula diet, 6 weeks of gradual refeeding, and 6 weeks of caloric stabilization at 5020-6280 kJ/day (1200-1500 Cal/day). Obese subjects were evaluated twice: before caloric restriction and during the last 3 weeks of caloric stabilization with a 3-h evening 1 microg/kg ovine CRH (oCRH) stimulation test. CRH-stimulated ACTH and cortisol values were compared to those of a control group of 12 normal weight women. Before caloric restriction, both ACTH and cortisol responses to oCRH were similar in obese women and normal weight controls. Weight loss did not significantly alter the ACTH response to oCRH; however, the total plasma cortisol response to oCRH decreased significantly with weight loss (area under the curve, 96,320 +/- 21,040 nmol/L x min before weight loss; 82,450 +/- 22,460 nmol/L x min after weight loss; P < 0.001). Cortisol-binding globulin also decreased significantly after weight loss (2,270 +/- 1,050 nmol/L) compared either to values obtained before weight loss (3,590 +/- 1,360 nmol/L; P < 0.001) or to those of normal weight controls (3,910 +/- 1,400 nmol/L; P < 0.001). Assay for plasma free cortisol, either before or 180 min after oCRH treatment, showed no significant changes in cortisol responses resulting from weight loss. As plasma free cortisol was not altered by weight reduction, the decrease in the total cortisol response to oCRH after weight loss appears to be secondary to significant decreases in cortisol-binding globulin. We conclude that when obese women lose large amounts of weight with a 3350 kJ/day, very low energy diet, such weight reduction does not significantly affect the HPA axis.     

Concurrent pharmacokinetic analysis of plasma cocaine and adrenocorticotropic hormone in men

The purpose of this study was to determine the covariance between plasma cocaine and ACTH pharmacokinetics. Twelve healthy male occasional cocaine users participated in a double blind study. Intravenous cocaine (0.2 mg/kg) or placebo was infused over 1 min, and samples for cocaine, ACTH and cortisol analysis were collected at 2, 4, 8, 12, 16, 20, 30, 40, 60, 80, 120, 180, and 240 min. Peak cocaine plasma levels averaged 101.2 +/- 14.6 ng/mL. ACTH increases were significantly correlated (P < 0.0001) with increases in plasma cocaine levels (r = 0.67; r2 = 0.44). Pharmacokinetic analysis showed that the t(max) (observed time to maximum concentration) values for cocaine (6.0 +/- 1.4 min) and ACTH (7.3 +/- 1.2 min) were almost identical. The area under the curve was calculated using the trapezoidal rule. The area under the curve for plasma cocaine was 6463 +/- 1070 ng/min x mL, and the area under the curve for ACTH was 1873 +/- 188 pmol/min x L. The mean half-life for plasma cocaine was 46.7 +/- 4.0 min, and that for ACTH was 35.8 +/- 5.1 min. Cardiovascular and subjective effect measures were correlated with concurrent increases in plasma cocaine and ACTH levels.     

The effect of vitamin E on cortisol and lactate levels and on the acid-base equilibrium in calves exposed to transportation stress

The objective of this study was to examine the effect of vitamin E administration on plasma levels of cortisol and lactate, and on acid base balance in transported calves. In the study, eight calves, aged approx. ten days, divided into two groups, were used. 20 mg of tocopherol-acetate per kg body weight were administered orally to each of the four experimental calves 24 hours before loading. The calves were transported by road for 3 hours. Blood samples collected before and after the transportation were examined for acid base balance, lactate, and plasma vitamin E and cortisol levels. The administration of vitamin E led to a decrease of cortisol levels in 24 hours (from 7.6 +/- 9.5 to 4.2 +/- 0.2 nmol/l) as well as to a significant increase (p < 0.05) of plasma vitamin E levels 26 h after administration (from 2.52 +/- 1.36 to 12.28 +/- 6.14 mumol/l). There was no difference between the groups in cortisol response due to transportation stress (Tab. III). The transportation caused typical stress changes in lactate levels and acid base balance (lactacidaemia and the tendency to acidosis, Tab. III, IV). There was approx. threefold increase in plasma lactate concentrations due to transportation (from 2.49 +/- 0.69 to 6.35 +/- 3.75 mmol/l). The results of the present study demonstrated metabolic changes which has been reported to be typical of mild physiological stress reaction. In the present study, vitamin E had no significant effect on plasma levels of cortisol, and lactate, and acid-base balance.     

Functioning of the porcine pituitary-adrenocortical axis during neonatal development

A study was conducted with neonatal boars to measure age-related changes in functioning of the pituitary-adrenocortical axis. Pigs were randomly assigned to control (n = 7-10/age) or treated (1-min restraint, n = 9-11/age) groups to be sampled at either 12, 19, or 26 days of age. Blood samples were taken via catheter 10 min before and 3, 10, and 20 min after restraint or at similar time intervals in controls. One day later, pigs were killed and adrenal glands obtained for ACTH receptor measurements. Basal plasma ACTH concentrations were greatest (p = 0.035) on day 12 when compared with later ages, but basal plasma cortisol concentrations were comparable at the three ages. Compared with controls, restraint elevated incremental plasma ACTH and cortisol responses at each age (p < 0.004). On day 12, maximal plasma ACTH (p = 0.0006) and incremental cortisol (p < 0.006) responses to restraint were greater than at later ages. Binding to adrenal ACTH receptors was greatest (p < 0.05) at day 13, which may help explain the apparently increased in vivo response of the adrenal gland to ACTH at this time. Restrained pigs had increased growth rates with increasing age (p = 0.016) whereas growth rates for control pigs did not differ with age. At day 27, 24 h after the 1-min restraint, body weights of restrained pigs exceeded those of control pigs (p = 0.045). At day 20, adrenal DNA and protein in pigs restrained 24 h previously were greater than in control pigs (p < 0.05). These data suggest age-related changes in functioning of the pituitary-adrenal axis in neonatal boars, and an absence of period during neonatal life when the porcine pituitary adrenocortical axis cannot respond to a stressor. The data also indicate both rapid and long-term responses of the adrenal to a very modest stressor and suggest an extreme sensitivity of neonatal pigs to environmental perturbations.     

Plasma cortisol responses after intramuscular corticotropin 1-24 in healthy men

Intravenous infusion of corticotropin 1-24 (ACTH 1-24) followed by a plasma cortisol measurement after 60 minutes of less than 20 microg/dL indicates clinically important glucocorticoid deficiency. In this study, we evaluated the morning plasma cortisol response to an intramuscular (IM) injection of ACTH 1-24 (250 microg) in 64 healthy men. Plasma cortisol increased significantly 30 and 60 minutes after IM ACTH 1-24 (P < .0001). In most subjects, a maximal response was obtained at 60 minutes. The cortisol response correlated positively with the morning basal cortisol concentration. The lowest cortisol peak and the lowest increment observed after IM ACTH 1-24 were, respectively, 12.6 and 3.5 microg/dL after 30 minutes and 16.3 and 5.3 microg/dL after 60 minutes. We conclude that a plasma cortisol level less than 16.0 microg/dL 60 minutes after IM ACTH 1-24 can be used as an index of glucocorticoid deficiency.     

Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone treatment

Evidence from animal as well as human studies has suggested that significant sex differences exist in hypothalamus-pituitary-adrenal axis (HPA) activity. As gonadal steroids could be important modulators of HPA sex differences, stress responses were investigated in subjects of advanced age after dehydroepiandrosterone (DHEA) or placebo treatment. After a 2-week treatment with 50 mg DHEA daily or placebo, 75 men and women (mean age, 67.6 yr) were exposed to the Trier Social Stress Test (TSST). The TSST is a brief psychosocial stress that consists of a free speech and mental arithmetic task in front of an audience. The results show that the TSST induced significant increases in ACTH, salivary free cortisol, total plasma cortisol, norepinephrine, and heart rates (all P < 0.0001) as well as decreased positive affect in the elderly (P = 0.0009). Men showed larger stress responses in ACTH (P = 0.004), salivary free cortisol (P = 0.044), and plasma total cortisol (P = 0.076) compared to women. No sex differences were observed in norepinephrine, epinephrine, or heart rate responses. In contrast to ACTH and cortisol response differences, women reported that they were significantly more stressed by the TSST than men (P = 0.0051). Women treated with DHEA showed ACTH stress responses similar to those of men, but significantly enhanced compared to those of women taking placebos (P < 0.009). No other stress response differences emerged between DHEA and placebo groups. Finally, DHEA treatment did not result in an improvement of subjective well-being. We conclude that elderly men show larger HPA responses than women to psychosocial stress, as studied in the TSST. Estrogen effects on hypothalamic CRF-producing neurons might be responsible for these sex differences.     

Hypofunction of the stress axis in Sj?gren's syndrome

OBJECTIVE: To examine the functional integrity of the hypothalamic-pituitary-adrenal (HPA) and thyroid axes in Sj?gren's syndrome (SS) via the assessment of basal and stimulated adrenocorticotropin (ACTH), cortisol, thyroid stimulating hormone (TSH), and prolactin levels. METHODS: Pituitary function of the HPA axis was assessed by determining the basal plasma levels of ACTH in the late afternoon, as well as the ACTH released to ovine corticotropin releasing hormone (oCRH) stimulation; adrenal function was assessed by measuring plasma cortisol levels in the late afternoon at baseline and after release of the endogenous ACTH during oCRH stimulation. Basal and thyrotropin releasing hormone (TRH) stimulated levels of TSH and prolactin were also assessed. Healthy volunteers were used as controls. RESULTS: Patients with SS, compared to controls, were characterized by significantly lower ACTH levels (pg/ml), (5.1 +/- 0.5 vs 11.4 +/- 1.5, respectively; p < 0.05) and cortisol levels (microg/ml), (2.4 +/- 0.6 vs 5.9 +/- 1.2, respectively; p < 0.05). Furthermore, a blunted pituitary and adrenal response to oCRH compared to controls was observed: peak plasma ACTH and cortisol levels for patients with SS were 46.2 +/- 5.4 pg/ml and 15.7 +/- 1.6 microg/ml, respectively, and for controls 61.5 +/- 3.8 and 19.6 +/- 0.7, respectively (p < 0.05). Basal TSH levels were significantly elevated in patients (1.3 +/- 0.3 microIU/ml vs 0.9 +/- 0.05 microIU/ml; p < 0.05). CONCLUSION: The above findings indicate hypoactivity of the HPA axis in patients with SS. Further studies are needed to definitively identify the locus of the defects and assess the significance of the pattern of the perturbations to the pathogenesis and expression of SS.     

Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs

To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five awake dogs. Four hours after endotoxin or saline challenge human corticotrophin-releasing hormone (hCRH; 1.0 microgram/kg) was administered. Plasma ACTH and cortisol levels increased considerably in response to endotoxin, from 13 +/- 1 ng/l to 360 +/- 85 ng/l (p < 0.01) and from 60 +/- 20 nmol/l to 710 +/- 80 nmol/l (p < 0.01). Despite a considerable difference in ACTH and cortisol levels prior to CRH administration between both studies (p < 0.01), the absolute increase in ACTH levels induced by hCRH was not different (231 +/ 43 ng/l vs 238 +/- 45 ng/l, control vs endotoxin). Plasma cortisol levels increased significantly in the control study (from 40 +/- 10 nmol/l to 330 +/- 40 nmol/l, p < 0.01), whereas they did not change in the endotoxin study after hCRH administration (from 710 +/- 80 nmol/l to 730 +/- 70 nmol/l, ns). We conclude that the HPA-axis reacts initially to endotoxin in such a way that cortisol, but not ACTH, secretion is maximized. Therefore, a blunted cortisol response to CRH testing is part of the initial response to infection.     

Use of an AC induction motor system for producing finger movements in human subjects

Cushing's disease appears as a functionally heterogeneous disease, but criteria that are able to distinguish between different clinical forms remain elusive. We compared two subgroups of patients with proven Cushing's disease according to the size of the pituitary adenoma, evaluated by computed tomography or magnetic resonance imaging. Our series comprised 11 patients with a microadenoma and 10 with a macroadenoma (median volumes (range): 173 (13-270) and 3022 (500-10312) mm3 respectively; P < 0.0001). The clinical presentation was similar in the two groups, but the time elapsed before diagnosis was longer, and visual impairment was less frequent in the patients with a microadenoma (1.5+/-0.8 years and 0%) than in those with a macroadenoma (0.7+/-0.6 years and 40%; P < 0.05). Morning and evening peripheral concentrations of ACTH were greater in patients with macroadenoma (134+/-78 and 130+/-7 ng/l respectively) than in those with microadenoma (52+/-28 and 56+/-19 ng/l, P < 0.05). Hypokalaemia and lymphopenia were also more pronounced in patients with macroadenoma (3.4+/-0.3 mmol/l and 1273+/-401 lymphocytes/mm3) than in those with microadenoma (3.8+/-0.3 mmol/l and 1852+/-668 lymphocytes/mm3 P < 0.05), although morning and evening plasma cortisol concentrations were similar in both groups. In patients with macroadenoma, there was less relative nycthemeral variation of ACTH concentrations (28+/-24%, compared with 62+/-39% in those with microadenoma; P < 0.05), less suppression of plasma cortisol by high doses of dexamethasone (-30+/-14%, compared with -61+/-25%; P < 0.05), and a reduced concentration ratio of mean basal cortisol to ACTH (7+/-3, compared with 12+/-5; P < 0.05). Plasma IGF-I concentration and the TSH peak response to TRH were significantly lower in patients with macroadenoma than in those with microadenoma (0.4+/-0.2 x 10(3) IU/I and 2.3+/-1.8 mIU/I, compared with 1.8+/-0.6 x 10(3) IU/I and 5.2+/-1.6 mUI/l; P < 0.05). Thus, in comparison with microadenomas, corticotroph macroadenomas are characterized by a greater and more autonomous ACTH secretion, inducing more pronounced biological signs of hypercorticism, and are more often accompanied by visual field defects and impairment of other pituitary hormonal secretions.