Biomedical subjects

B J Canny

Publications and source records attributed to B J Canny.

At least 19 recordsLinked to original sources

PubMed2003

Force-matching errors after eccentric exercise attributed to muscle soreness.

1. Experiments were performed to test the ability of human subjects to match forces in their elbow flexor muscles following eccentric exercise of one arm and, in a second series, after biceps brachii of one arm had been made sore by injection of hypertonic saline. 2. In the force-matching task, the elbow flexors of one arm, the reference arm, generated 30% of maximum voluntary contraction (MVC) under visual control. Subjects matched that level with their other arm, the indicator arm, without visual feedback. 3. After eccentric exercise of elbow flexors of the indicator arm, subjects felt they had achieved a satisfactory match while indicating forces that were significantly lower, by approximately 5%, than the reference level. Errors were in the opposite direction (i.e. forces were overestimated) when the reference arm was exercised. 4. Errors were reduced when matching forces were expressed as fractions of the sessional MVC rather than the pre-exercise MVC. Residual errors from 24 h postexercise onwards were attributed to muscle soreness from the exercise. 5. In support of this view, a similar pattern of matching errors was observed when an unexercised arm was made sore by injection of hypertonic saline into the biceps. 6. It is concluded that muscle soreness can interfere with a subject's ability to match forces, perhaps as a result of a reduced excitability of motor cortex. It implies that muscle soreness may contribute to the weakness experienced after a period of unaccustomed eccentric exercise.

Electromyography↗

PubMed2003

Force matching at the elbow joint is disturbed by muscle soreness.

These experiments are concerned with the ability of human subjects to match isometric torque in their elbow flexor muscles when biceps of one arm is made sore. Pain was induced by injection of hypertonic saline. Subjects were asked to generate a level of torque, 30% of maximum, with one arm, the reference arm. To achieve the required torque, subjects were given visual feedback. Subjects were then asked to match this torque with their other arm, the indicator arm. In control measurements, subjects were consistent in their matching ability and often were quite accurate. However, when biceps of one arm was made sore, subjects consistently and significantly underestimated the level of torque being generated by the sore arm. Painful heat applied to the skin over biceps produced a similar pattern of errors. Heating skin remote from elbow flexors had no significant effect. One interpretation of these findings is that the nociceptive input from the sore region of skin or muscle leads to reduced excitability of the motor cortex. That, in turn, disturbs the relationship between the centrally generated effort and motor output, leading to matching errors.

Adult↗

PubMed2002

Progressive increase in human skeletal muscle AMPKalpha2 activity and ACC phosphorylation during exercise.

The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protein kinase (AMPK)alpha1 and -alpha2 activity and acetyl-CoA carboxylase (ACCbeta) and neuronal nitric oxide synthase (nNOSmu) phosphorylation was investigated. Seven active healthy individuals cycled for 30 min at a workload requiring 62.8 +/- 1.3% of peak O(2) consumption (VO(2 peak)) with muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of exercise. AMPKalpha1 activity was not altered by exercise; however, AMPKalpha2 activity was significantly (P < 0.05) elevated after 5 min (approximately 2-fold), and further elevated (P < 0.05) after 30 min (approximately 3-fold) of exercise. ACCbeta phosphorylation was increased (P < 0.05) after 5 min (approximately 18-fold compared with rest) and increased (P < 0.05) further after 30 min of exercise (approximately 36-fold compared with rest). Increases in AMPKalpha2 activity were significantly correlated with both increases in ACCbeta phosphorylation and reductions in muscle glycogen content. Fat oxidation tended (P = 0.058) to increase progressively during exercise. Muscle creatine phosphate was lower (P < 0.05), and muscle creatine, calculated free AMP, and free AMP-to-ATP ratio were higher (P < 0.05) at both 5 and 30 min of exercise compared with those at rest. At 30 min of exercise, the values of these metabolites were not significantly different from those at 5 min of exercise. Phosphorylation of nNOSmu was variable, and despite the mean doubling with exercise, statistically significance was not achieved (P = 0.304). Western blots indicated that AMPKapproximately 2 was associated with both nNOSmu and ACCbeta consistent with them both being substrates of AMPKalpha2 in vivo. In conclusion, AMPKalpha2 activity and ACCbeta phosphorylation increase progressively during moderate exercise at approximately 60% of VO(2 peak) in humans, with these responses more closely coupled to muscle glycogen content than muscle AMP/ATP ratio.

AMP-Activated Protein Kinases↗

PubMed2002

Influence of sex and gonadal status of sheep on cortisol secretion in response to ACTH and on cortisol and LH secretion in response to stress: importance of different stressors.

There are sex differences in the response to stress and in the influence of stress on reproduction which may be due to gonadal steroids but the nature of these differences and the role of the gonads are not understood. We tested the hypotheses that sex and the presence/absence of gonads (gonadal status) will influence the cortisol response to injection of ACTH, insulin-induced hypoglycaemia and isolation/restraint stress, and that sex and gonadal status will influence the secretion of LH in response to isolation/restraint stress. Four groups of sheep were used in each of three experiments: gonad-intact rams, gonadectomised rams, gonad-intact ewes in the mid-luteal phase of the oestrous cycle and gonadectomised ewes. In Experiment 1 (n=4/group), jugular blood samples were collected every 10 min for 6 h; after 3 h, two animals in each group were injected (i.v.) with ACTH and the remaining two animals were injected (i.v.) with saline. Treatments were reversed 5 days later so that every animal received both treatments. Experiment 2 (n=4/group) used a similar schedule except that insulin was injected (i.v.) instead of ACTH. In Experiment 3 (n=5/group), blood samples were collected every 10 min for 16 h on a control day and again 2 weeks later when, after 8 h of sampling, all sheep were isolated and restrained for 8 h. Plasma cortisol was significantly (P<0.05) elevated following injection of ACTH or insulin and during isolation/restraint stress. There were no significant differences between the sexes in the cortisol response to ACTH. Rams had a greater (P<0.05) cortisol response to insulin-induced hypoglycaemia than ewes while ewes had a greater (P<0.05) cortisol response to isolation/restraint stress than rams. There was no effect of gonadal status on these parameters. Plasma LH was suppressed (P<0.05) in gonadectomised animals during isolation/restraint stress but was not affected in gonad-intact animals, and there were no differences between the sexes. Our results show that the sex that has the greater cortisol response to a stressor depends on the stressor imposed and that these sex differences are likely to be at the level of the hypothalamo-pituitary unit rather than at the adrenal gland. Since there was a sex difference in the cortisol response to isolation/restraint, the lack of a sex difference in the response of LH to this stress suggests that glucocorticoids are unlikely to be a major mediator of the stress-induced suppression of LH secretion.

Adrenocorticotropic Hormone↗

PubMed2001

Combined xylazine and ketamine as an analgesic regimen in sheep.

OBJECTIVE: To determine whether low dose xylazine with ketamine reduces the concentrations of cortisol and prolactin in sheep postoperatively and to characterise the effects of the drugs on behaviour during recovery. DESIGN: Analysis of variance was used to compare the effects of anaesthesia, surgery and combined ketamine/xylazine treatment on the plasma cortisol and prolactin concentrations and on behavioural variables in pregnant ewes subjected to abdominal surgery. PROCEDURE: Twelve ewes were randomly assigned to receive either ketamine/xylazine or placebo in association with anaesthesia and surgery. Both groups of ewes underwent anaesthesia alone followed a week later by anaesthesia with laparotomy and hysterotomy. Plasma cortisol and prolactin concentrations were assayed during these procedures and for 5 days afterwards. Behavioural observations were made remotely during recovery from anaesthesia and anaesthesia plus surgery. RESULTS: The concentrations of cortisol in the plasma of pregnant ewes undergoing surgery were increased by preoperative handling and the onset of thiopentone/halothane anaesthesia, with a further increase during surgery (P = 0.033). Cortisol concentrations decreased over the first four postoperative hours (P = 0.029) and were normal by 24 h. The drug treatment did not affect the immediate responses of ewes to anaesthesia or surgery, although treated ewes had lower cortisol concentrations than saline-treated controls over the first five postoperative days (P = 0.018). Prolactin concentrations increased in response to anaesthesia (P = 0.047), but were not affected by surgery or the drug treatment. Drug-treated ewes had prolonged sleeping time after surgery (P = 0.002), but they took no longer to stand than saline-treated controls and required fewer attempts to stand successfully (P = 0.025). CONCLUSION: At the doses used, ketamine and xylazine did not mitigate the immediate endocrine consequences of surgery but the behavioural data provide a basis for further investigations that may lead to improvements in analgesic treatments.

Analgesics↗

PubMed2001

Differential effects of dexamethasone treatment on lipopolysaccharide-induced testicular inflammation and reproductive hormone inhibition in adult rats.

A single intraperitoneal injection of lipopolysaccharide (LPS) causes a biphasic suppression of testicular steroidogenesis in adult rats, with inhibition at 6 h and 18-24 h after injection. The inhibition of steroidogenesis is independent of the reduction in circulating LH that also occurs after LPS treatment, indicating a direct effect of inflammation at the Leydig cell level. The relative contributions to this inhibition by intratesticular versus systemic responses to inflammation, including the adrenal glucocorticoids, was investigated in this study. Adult male Wistar rats (eight/group) received injections of LPS (0.1 mg/kg i.p.), dexamethasone (DEX; 50 microg/kg i.p.), LPS and DEX, or saline only (controls), and were killed 6 h, 18 h and 72 h later. Treatment with LPS stimulated body temperature and serum corticosterone levels measured 6 h later. Administration of DEX had no effect on body temperature, but suppressed serum corticosterone levels. At the dose used in this study, DEX alone had no effect on serum LH or testosterone at any time-point. Expression of mRNA for interleukin-1beta (IL-1beta), the principal inflammatory cytokine, was increased in both testis and liver of LPS-treated rats. Serum LH and testosterone levels were considerably reduced at 6 h and 18 h after LPS treatment, and had not completely recovered by 72 h. At 6 h after injection, DEX inhibited basal IL-1beta expression and the LPS-induced increase of IL-1beta mRNA levels in the liver, but had no effect on IL-1beta in the testis. The effects of DEX on IL-1beta levels in the liver were no longer evident by 18 h. In LPS-treated rats, DEX caused a significant reversal of the inhibition of serum LH and testosterone at 18 h, although not at 6 h or 72 h. Accordingly, DEX inhibited the systemic inflammatory response, but had no direct effect on either testicular steroidogenesis or intra-testicular inflammation, at the dose employed. These data suggest that the inhibition of Leydig cell steroidogenesis at 6 h after LPS injection, which was not prevented by co-administration of DEX, is most likely due to direct actions of LPS at the testicular level. In contrast, the later Leydig cell inhibition (at 18 h) may be attributable to extra-testicular effects of LPS, such as increased circulating inflammatory mediators or the release of endogenous glucocorticoids, that were inhibited by DEX treatment. These data indicate that the early and late phases of Leydig cell inhibition following LPS administration are due to separate mechanisms.

Analysis of Variance↗

PubMed2001

The role of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins essential for adrenal steroidogenesis in the late-gestation ovine fetus.

To further understand the relative roles of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins that are essential for adrenal development, we investigated the effects of, first, an ACTH infusion and labour in intact fetuses and, secondly, the effect of an ACTH infusion to fetuses with and without a pituitary gland, on the relative abundance of the mRNA encoding for the ACTH receptor (MC2R), steroidogenic factor 1 (SF-1), cholesterol side-chain cleavage enzyme (P450(scc)), 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17alpha-hydroxylase (P450(C17)) in the fetal adrenal gland. ACTH(1-24) infusion (14.7 pmol/kg per h) to intact fetuses was without effect on the abundance of mRNA encoding MC2R and SF-1, irrespective of whether the infusion was given for 18 (115-132 days of gestation) or 32 days (115 days to term (147 days of gestation)). Hypophysectomy (HX) did not alter the expression of MC2R mRNA; however, the abundance of SF-1 mRNA fell by approximately 50% following the removal of the pituitary gland. ACTH(1-24) infusion to HX fetuses failed to restore levels of SF-1 mRNA to that seen in intact animals. P450(scc) and 3betaHSD mRNAs were increased by ACTH(1-24) infusion for 18 days in intact animals, although no effects of the infusion were seen on P450(C17) mRNA levels. For all three of these mRNAs, there was a significant increase in their abundance between 132 days of gestation and term in intact fetuses. By term, ACTH(1-24) infusion was without any additional effect on their abundance. HX decreased the expression of P450(scc), 3betaHSD and P450(C17) mRNAs, while ACTH(1-24) infusion to HX fetuses increased the expression of these mRNAs to levels seen in intact animals. There were significant correlations between the abundance of the mRNA for P450(scc), 3betaHSD and P450(C17), but not MC2R and SF-1, and premortem plasma cortisol concentrations. These results emphasise the importance of the pituitary gland and ACTH in the regulation of the enzymes involved in adrenal steroidogenesis. Factors in addition to ACTH may also play some role, as the infusion was not always effective in increasing the abundance of the mRNAs. Surprisingly, the mRNA for MC2R and SF-1 did not appear to be regulated by ACTH in the late-gestation ovine fetus, though a pituitary-dependent factor may be involved in the regulation of SF-1 mRNA abundance.

Adrenal Glands↗

PubMed2000

AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation.

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing protein kinase responsible for coordinating metabolism and energy demand. In rodents, exercise accelerates fatty acid metabolism, enhances glucose uptake, and stimulates nitric oxide (NO) production in skeletal muscle. AMPK phosphorylates and inhibits acetyl-coenzyme A (CoA) carboxylase (ACC) and enhances GLUT-4 translocation. It has been reported that human skeletal muscle malonyl-CoA levels do not change in response to exercise, suggesting that other mechanisms besides inhibition of ACC may be operating to accelerate fatty acid oxidation. Here, we show that a 30-s bicycle sprint exercise increases the activity of the human skeletal muscle AMPK-alpha1 and -alpha2 isoforms approximately two- to threefold and the phosphorylation of ACC at Ser(79) (AMPK phosphorylation site) approximately 8.5-fold. Under these conditions, there is also an approximately 5.5-fold increase in phosphorylation of neuronal NO synthase-mu (nNOSmu;) at Ser(1451). These observations support the concept that inhibition of ACC is an important component in stimulating fatty acid oxidation in response to exercise and that there is coordinated regulation of nNOSmu to protect the muscle from ischemia/metabolic stress.

AMP-Activated Protein Kinases↗

PubMed2000

Effect of carbohydrate ingestion on glucose kinetics and muscle metabolism during intense endurance exercise.

There has been recent interest in the potential performance and metabolic effects of carbohydrate ingestion during exercise lasting approximately 1 h. In this study, 13 well-trained men ingested in randomized order either a 6% glucose solution (CHO trial) or a placebo (Con trial) during exercise to exhaustion at 83+/-1% peak oxygen uptake. In six subjects, vastus lateralis muscle was sampled at rest, at 32 min, and at exhaustion, and in six subjects, glucose kinetics was determined by infusion of [6,6-(2)H]glucose in both trials and ingestion of [6-(3)H]glucose in the CHO trial. Of the 84 g of glucose ingested during exercise in the CHO trial, only 22 g appeared in the peripheral circulation. This resulted in a small (12 g) but significant (P<0.05) increase in glucose uptake without influencing carbohydrate oxidation, muscle glycogen use, or time to exhaustion (CHO: 68.1+/-4.1 min; Con: 69.6+/-5.5 min). Decreases in muscle phosphocreatine content and increases in muscle inosine monophosphate and lactate content during exercise were similar in the two trials. Although endogenous glucose production during exercise was partially suppressed in the CHO trial, it remained significantly above preexercise levels throughout exercise. In conclusion, only 26% of the ingested glucose appeared in the peripheral circulation. Glucose ingestion increased glucose uptake and partially reduced endogenous glucose production but had no effect on carbohydrate oxidation, muscle metabolism, or time to exhaustion during exercise at 83% peak oxygen uptake.

Adenosine Diphosphate↗

PubMed1999

Adrenal responsiveness and the timing of parturition in hypothalamo-pituitary disconnected ovine foetuses with and without constant adrenocorticotrophin infusion.

Ovine parturition results from an increase in foetal cortisol secretion in late gestation which is dependent on an intact hypothalamo-pituitary connection. The cortisol surge and parturition fails in hypothalamo-pituitary disconnected (HPD) foetuses but, paradoxically, immunoreactive (ir)-ACTH concentrations and secretory dynamics appear normal. This study compares the occurrence and timing of labour, basal ir-ACTH and cortisol concentrations and adrenal responsiveness in HPD foetuses (HPD/ACTH) receiving constant ACTH(1-24) infusion (43 ng/h/kg) from surgery (114+/-1 days gestational age (GA)) with those of saline-infused HPD or intact foetuses (HPD/SAL and INT/SAL). HPD/ACTH foetuses initiated labour at 147+/-2 days GA, which was not significantly different from INT/SAL foetuses (149+/-1 day GA). HPD/SAL foetuses were killed electively at 146+/-3 days GA with no signs of labour. Foetal ir-ACTH concentrations in all groups were indistinguishable, but only HPD/ACTH and INT/SAL foetuses had a significant cortisol surge. Adrenal responsiveness to ACTH(1-24)(1 microg/kg) was greater in HPD/ACTH foetuses than in HPD/SAL or INT/SAL foetuses at all GAs studied. Adrenal responsiveness in HPD/SAL foetuses exceeded that in INT/SAL foetuses at 120 and 130 days GA but did not change with GA. In summary, the basal cortisol and parturition defect in HPD foetuses was reversed by low-dose ACTH(1-24) infusion. Basal cortisol concentrations were unrelated to adrenal responsiveness. HPD/SAL foetuses had hyper-responsive adrenals compared to those of INT/SAL foetuses until 130 days GA, suggesting that the foetal hypothalamus exerts a negative influence on adrenal cortisol responses before 130 days GA, after which time stimulatory influences predominate.

Adrenal Glands↗

PubMed1999

Sustained but not repeated acute elevation of cortisol impaired the luteinizing hormone surge, estrus, and ovulation in gilts.

We tested the hypothesis that sustained and repeated acute elevation of cortisol would impair the LH surge, estrus, and ovulation in gilts. Cortisol was injected intramuscularly, to achieve a sustained elevation of plasma concentrations of cortisol, or intravenously, to achieve an acute elevation of plasma concentrations of cortisol. Control gilts received i.m. injections of oil and i.v. injections of saline. These treatments were administered to gilts (n = 6 per treatment) at 12-h intervals from Days 7 to 11 of the estrous cycle until after estrus ceased or until Day 27 or 28 of the estrous cycle, whichever came first. The repeated acute elevation of cortisol had no effect on the LH surge, estrus, or ovulation. In contrast, when the elevation of cortisol was sustained, the LH surge, estrus, and ovulation were inhibited. We conclude that cortisol is capable of direct actions to impair reproductive processes in female pigs but that plasma concentrations of cortisol need to be elevated for a substantial period for this to occur.

Animals↗

PubMed1999

Fluid ingestion does not influence intense 1-h exercise performance in a mild environment.

PURPOSE: It is generally recommended that fluid be ingested during exercise at a rate that prevents body mass loss and prevents dehydration. It is, however, not known whether these recommendations are valid during intense endurance exercise in a mild environment. The purpose of this study was to examine the effect of fluid ingestion volume on heart rate (HR), rectal temperature, plasma electrolytes, and performance during intense endurance exercise at 21 degrees C. METHODS: Eight well-trained men (26+/-1 yr; 79.6+/-3.5 kg; VO2peak = 5.05+/-0.17 L.min(-1) ; mean+/-SEM) cycled for 45 min at 80+/-1% VO2peak while receiving either no fluid replacement (NF), a volume of water that prevented body mass loss (FR-100 = 1.47+/-0.05 L), or 50% of this volume (FR-50 = 0.72+/-0.03 L). The 45-min exercise bout was followed immediately by a 15-min "all-out" performance ride. RESULTS: NF was associated with a 1.9+/-0.0% body mass loss, while FR-50 and FR-100 resulted in losses of 1.0 = 0.1% and 0.0+/-0.1%, respectively. Although values tended to be higher in NF, fluid ingestion had no significant effect on HR or rectal temperature during exercise. Reductions in plasma volume and increases in plasma sodium and potassium concentrations during exercise were largely unaffected by fluid ingestion. RPE increased to a similar extent during exercise in the three trials while a mild increase in the degree of stomach bloating/fullness was evident in FR-100. Work completed during the 15-min performance ride was similar in the three trials (NF: 273+/-8, FR-50: 267+/-8, FR-100: 269+/-9 kJ). CONCLUSIONS: There appears to be little benefit from ingesting water during intense 1-h cycling exercise in mild environmental conditions since such ingestion has no significant effect on HR, body temperature, plasma volume, plasma electrolytes, or performance.

Adult↗

PubMed1999

Central administration of leptin to ovariectomized ewes inhibits food intake without affecting the secretion of hormones from the pituitary gland: evidence for a dissociation of effects on appetite and neuroendocrine function.

We have studied the effect of leptin on food intake and neuroendocrine function in ovariectomized ewes. Groups (n = 5) received intracerebroventricular infusions of either vehicle or leptin (20 microg/h) for 3 days and were blood sampled over 6 h on days -1, 2, and for 3 h on day 3 relative to the onset of the infusion. The animals were then killed to measure hypothalamic neuropeptide Y expression by in situ hybridization. Plasma samples were assayed for metabolic parameters and pituitary hormones. Food intake was reduced by leptin, but did not change in controls. Leptin treatment elevated plasma lactate and nonesterified fatty acids, but did not affect glucose or insulin levels, indicating a state of negative energy balance that was met by the mobilization of body stores. Pulse analysis showed that the secretion of LH and GH was not affected by leptin treatment, nor were the mean plasma concentrations of FSH, PRL, or cortisol. Expression of messenger RNA for neuropeptide Y in the arcuate nucleus was reduced by the infusion of leptin, primarily due to reduced expression per cell rather than a reduction in the number of cells observed. Thus, the action of leptin to inhibit food intake is dissociated from neuroendocrine function. These results suggest that the metabolic effects of leptin are mediated via neuronal systems that possess leptin receptors rather than via endocrine effects.

Animals↗

PubMed1999

Suppression of the secretion of luteinizing hormone due to isolation/restraint stress in gonadectomised rams and ewes is influenced by sex steroids.

In this study we used an isolation/restraint stress to test the hypothesis that stress will affect the secretion of LH differently in gonadectomised rams and ewes treated with different combinations of sex steroids. Romney Marsh sheep were gonadectomised two weeks prior to these experiments. In the first experiment male and female sheep were treated with vehicle or different sex steroids for 7 days prior to the application of the isolation/restraint stress. Male sheep received either i.m. oil (control rams) or 6 mg testosterone propionate injections every 12 h. Female sheep were given empty s.c. implants (control ewes), or 2x1 cm s.c. implants containing oestradiol, or an intravaginal controlled internal drug release device containing 0.3 g progesterone, or the combination of oestradiol and progesterone. There were four animals in each group. On the day of application of the isolation/restraint stress, blood samples were collected every 10 min for 16 h for the subsequent measurement of plasma LH and cortisol concentrations. After 8 h the stress was applied for 4 h. Two weeks later, blood samples were collected for a further 16 h from the control rams and ewes, but on this day no stress was imposed. In the second experiment, separate control gonadectomised rams and ewes (n=4/group) were studied for 7 h on 3 consecutive days, when separate treatments were applied. On day 1, the animals received no treatment; on day 2, isolation/restraint stress was applied after 3 h; and on day 3, an i. v. injection of 2 microg/kg ACTH1-24 was given after 3 h. On each day, blood samples were collected every 10 min and the LH response to the i.v. injection of 500 ng GnRH administered after 5 h of sampling was measured. In Experiment 1, the secretion of LH was suppressed during isolation/restraint in all groups but the parameters of LH secretion (LH pulse frequency and amplitude) that were affected varied between groups. In control rams, LH pulse amplitude, and not frequency, was decreased during isolation/restraint whereas in rams treated with testosterone propionate the stressor reduced pulse frequency and not amplitude. In control ewes, isolation/restraint decreased LH pulse frequency but not amplitude. Isolation/restraint reduced both LH pulse frequency and amplitude in ewes treated with oestradiol, LH pulse frequency in ewes treated with progesterone and only LH pulse amplitude in ewes treated with both oestradiol and progesterone. There was no change in LH secretion during the day of no stress. Plasma concentrations of cortisol were higher during isolation/restraint than on the day of no stress. On the day of isolation/restraint maximal concentrations of cortisol were observed during the application of the stressor but there were no differences between groups in the magnitude of this response. In Experiment 2, isolation/restraint reduced the LH response to GnRH in rams but not ewes and ACTH reduced the LH response to GnRH both in rams and ewes. Our results show that the mechanism(s) by which isolation/restraint stress suppresses LH secretion in sheep is influenced by sex steroids. The predominance of particular sex steroids in the circulation may affect the extent to which stress inhibits the secretion of GnRH from the hypothalamus and/or the responsiveness of the pituitary gland to the actions of GnRH. There are also differences between the sexes in the effects of stress on LH secretion that are independent of the sex steroids.

Adrenocorticotropic Hormone↗

PubMed1999

The influence of sex and gonadectomy on the hypothalamo-pituitary-adrenal axis of the sheep.

There is a sex difference in the hypothalamo-pituitary-adrenal (HPA) axis of many species, although there are sparse data on the sheep. In the present study we have compared the HPA axes of intact and gonadectomised adult male and female sheep at the level of the median eminence, pituitary and adrenal glands using a variety of in vitro approaches. The concentration of arginine vasopressin (AVP) was higher (P<0.01) in the median eminence of male than female sheep, and was also elevated by gonadectomy of either sex (P<0.01). The concentration of corticotrophin-releasing factor (CRF) in the median eminence did not differ between the sexes, but was also elevated in both sexes following gonadectomy (P<0.01). Anterior pituitary pro-opiomelanocortin mRNA concentrations were higher (P<0.05) in intact male sheep than in intact females, with the levels in gonadectomised animals of both sexes being intermediate. In contrast to this finding, basal ACTH secretion from anterior pituitary cells was higher (P<0.05) in cultures derived from female sheep than those from males, but gonadectomy was without effect. There was no effect of sex or gonadectomy on in vitro ACTH secretion in response to AVP, CRF or the combination of AVP and CRF, and in all cases the combination of AVP and CRF generated greater (P<0.0001) ACTH secretion than AVP alone. AVP alone was more effective (P<0.01) than CRF alone as an ACTH secretagogue. The adrenal glands were larger (P<0.05) in female than male sheep, with no effect of gonadectomy. Basal cortisol production was greatest (P<0.05) in cultures of adrenal cells from intact male sheep, though ACTH- and 8BrcAMP-induced cortisol production was greater in the cultures of cells from females (P=0.05); there were no effects of gonadectomy. Cultures of adrenocortical cells from male sheep had greater (P<0.05) basal cAMP production, but ACTH-stimulated cAMP production did not differ between any of the groups of animals. These findings show a range of differences in the HPA axis of male and female sheep. Furthermore, they suggest that the heightened activity of the axis in the female occurs primarily due to differences at the level of the adrenal gland, and that greater adrenal responsiveness of female animals is due to differences in the latter stages of steroidogenesis, rather than an effect on ACTH signal transduction at its receptor.

Adrenal Glands↗

PubMed1999

Central administration of corticotrophin releasing hormone but not arginine vasopressin stimulates the secretion of luteinizing hormone in rams in the presence and absence of testosterone.

This study tested the hypothesis that central administration of corticotrophin-releasing hormone (CRH) and/or arginine vasopressin (AVP) will affect the secretion of LH in rams and that testosterone is necessary for these actions to occur. Plasma LH levels were measured in castrated rams during 1 h infusion of either 100 microliter vehicle/mock cerebrospinal fluid (CSF) or mock CSF containing 25 microgram CRH, 25 microgram AVP or 25 microgram of each peptide through guide cannulae into the third cerebral ventricle. These intracerebroventricular (i.c.v.) infusions were given to the castrated rams following injections (i.m.) each 12 h of oil or 8 mg testosterone propionate for 7 days. Blood samples were collected every 10 min for 4 h before i.c.v. infusion, during infusion and for 4 h following the infusion. Infusion of vehicle did not affect any endocrine parameters. In contrast, the plasma concentrations of LH and the amplitude of LH pulses were increased significantly during and following infusion of CRH, and this effect was not influenced by whether the castrated rams were treated with testosterone propionate or whether the CRH was administered in combination with AVP. Infusion of AVP alone did not affect LH secretion. The frequency of LH pulses and the plasma concentrations of FSH did not change with any of the i.c.v. treatments. The plasma concentrations of cortisol were significantly increased by CRH and AVP infusions. The plasma concentrations of cortisol achieved during and following i.c.v. infusion of CRH and AVP combined were greater than the concentrations achieved as a result of treatment with AVP alone but were similar to those with CRH. There was no effect of testosterone propionate on cortisol levels. These results show that CRH, but not AVP, is capable of acting either centrally or at the pituitary level to increase the secretion of LH in rams and these actions are not affected by testosterone. The stimulatory effects of CRH on LH secretion are to increase the amplitude of GnRH pulses and/or the responsiveness of the pituitary to the actions of GnRH with no effect on the frequency of GnRH pulses. The secretion of FSH in rams is not influenced by either CRH or AVP. The effect of CRH to increase LH pulse amplitude occurs in the face of increased cortisol levels, further reinforcing our belief that this adrenal steroid does not affect the reproductive axis in this species.

Animals↗

PubMed1999

Inhibition of the secretion of LH in ovariectomised pigs by sustained but not repeated acute elevation of cortisol in the absence but not the presence of oestradiol.

Prolonged stress is known to impair reproduction. It has been proposed that reproduction will also be impaired when a severe acute stress occurs during a period of elevated plasma concentrations of oestradiol, such as during the follicular phase of the oestrous cycle. In this experiment, we hypothesised that repeated acute and sustained elevation of cortisol would suppress the secretion of LH in ovariectomised pigs and that these effects would be enhanced in the presence of oestradiol negative feedback. Cortisol (or vehicle) was administered 12 hourly to ovariectomised pigs (n=6/treatment) for 8 days in the absence of oestradiol treatment and for a further 8 days during treatment with oestradiol. Vehicle was administered to 'control' pigs, 10 or 20 mg cortisol was administered i.v. to pigs to produce 'repeated acute' elevation of cortisol and 250 mg cortisol was administered i.m. to pigs to give a 'sustained' elevation of cortisol. Both before and during treatment with oestradiol, plasma concentrations of LH were monitored on the day before treatment, on the 4th and 8th days of treatment and following an i.v. injection of GnRH at the end of the 8th day of treatment. The repeated acute elevation of cortisol did not impair any parameters of LH secretion (i.e. mean plasma concentrations of LH, pulse amplitude or frequency, pre-LH pulse nadir or the LH response to GnRH) in the absence or in the presence of oestradiol. In contrast, when the elevation of cortisol was sustained, the mean plasma concentrations of LH and the pre-LH pulse nadir were significantly (P<0.05) lower on the 8th day of treatment than on the day before treatment and on the 4th day of treatment. Nevertheless, no other parameters of LH secretion were affected and these effects only occurred in the absence (not in the presence) of oestradiol. In conclusion, cortisol needed to be elevated for more than 4 days to impair the secretion of LH, and oestradiol did not enhance the impact of cortisol on LH secretion in ovariectomised pigs.

Animals↗

PubMed1998

The effect of repeated boar exposure on cortisol secretion and reproduction in gilts.

It has been proposed that short-term activation of the hypothalamo-pituitary adrenal axis, with a consequent increase in the secretion of cortisol, amy disrupt the endocrine events prior to ovulation and thereby impair reproduction in females. We investigated this concept in gilts in which oestrus was detected by introduction to boars, where intense physical contact is possible, or by applying pressure to the back of gilts (back-pressure test) during fence-line exposure to boars, where intense physical contact is prohibited. We expected that there would be a greater release of cortisol and that reproduction would be inhibited in gilts introduced to boars compared to gilts in which the back-pressure test was used. As expected, introduction of gilts to boars resulted in a significant transient increase in plasma concentrations of cortisol while there was no significant effect of using the back-pressure test on plasma cortisol. Nevertheless, introduction of gilts to boars did not impair reproduction and there was no effect of method of detecting oestrus on duration of oestrus, sexual receptivity, fertility or fecundity. The length of the oestrous cycle was decreased and ovulation rate increased in gilts that were introduced to boars compared to gilts that underwent the back-pressure test, indicating that introduction of gilts to boars may have stimulated these aspects of reproduction. These stimulatory effects may have been due to an increased exposure of gilts to sexual behaviour and stimuli from boars when introduced to boars and/or to stimulatory effects of the hypothalamo-pituitary adrenal axis on some aspects of reproduction.

Adrenal Glands↗