Biomedical subjects

A J Tilbrook

Publications and source records attributed to A J Tilbrook.

At least 19 recordsLinked to original sources

PubMed2006

Neuroendocrine mechanisms of innate states of attenuated responsiveness of the hypothalamo-pituitary adrenal axis to stress.

Neuroendocrine responses to stress vary between sexes and reproductive states and are influenced by the type of stressor. Stress responses are attenuated in some physiological states, such as lactation and conditions of low visceral adipose tissue. Moreover, some individuals within a species characteristically display reduced stress responses. The neuroendocrine mechanisms for stress hyporesponsiveness are likely to include reduced synthesis and secretion of corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) from the hypothalamus as a result of enhanced glucocorticoid negative feedback and/or reduced noradrenergic stimulatory input from the brain stem. A major limitation of research to date is the lack of direct measures of CRH and AVP secretion. Attenuated stress responsiveness is also commonly associated with reduced pituitary responsiveness to CRH and AVP. The possible roles of inhibitory central inputs to CRH and AVP neurons and of oxytocin and prolactin in attenuating the HPA axis responses to stress are unknown.

Adaptation, Physiological↗

PubMed2006

Activation of the hypothalamo-pituitary-adrenal axis by isolation and restraint stress during lactation in ewes: effect of the presence of the lamb and suckling.

We investigated the effect of the presence and absence of lambs and suckling by lambs to attenuate activation of the hypothalamo-pituitary-adrenal (HPA) axis to isolation and restraint stress in lactating sheep. In experiment 1, blood samples were collected every 10 min from nonlactating (n = 5) and lactating (n = 5) ewes for 4 h before and during stress. In experiment 2, ewes (n = 6) were allocated to 1) nonlactating, 2) lactating with lambs absent, 3) lactating with lambs present but unable to suckle, and 4) lactating with lambs present and able to suckle. Blood samples were collected over 8 h with no stress (control day) and for 4 h before and 4 h during stress (stress day). In experiment 1, the mean (+/-SEM) cortisol concentrations increased significantly (P < 0.05) in nonlactating ewes during stress but did not change in lactating ewes. In experiment 2, cortisol did not vary on the control day or pretreatment of the stress day but increased (P < 0.05) during stress in all groups except lactating ewes with lambs present and able to suckle. The greatest cortisol response occurred in nonlactating ewes followed by lactating ewes with lambs absent and lactating ewes with lambs present but unable to suckle. During stress, the ACTH concentrations increased (P < 0.05) in nonlactating ewes and lactating ewes with lambs absent but not in lactating ewes with lambs present. We conclude that the activity of the HPA axis during isolation and restraint is reduced in lactating ewes and that the presence of lambs increases this level of attenuation.

Adrenocorticotropic Hormone↗

PubMed2006

A sex difference in the cortisol response to tail docking and ACTH develops between 1 and 8 weeks of age in lambs.

It is important to understand factors that may influence responses to stress, as these factors may also influence vulnerability to pathologies that can develop when stress responses are excessive or prolonged. It is clear that, in adults, the sex of an individual can influence the cortisol response to stress in a stressor specific manner. Nevertheless, the stage of development at which these sex differences emerge is unknown. We tested the hypothesis that there are sex differences in the cortisol response to tail docking and ACTH in lambs of 1 and 8 weeks of age. We also established cortisol responses in males when tail docking was imposed alone and in combination with castration at these ages. In experiment 1, 1 and 8 week old male and female lambs were subjected to sham handling, tail docking or, in males, a combination of tail docking and castration. In experiment 2, we administered ACTH (1.0 IU/kg) to male and female lambs at 1 and 8 weeks of age. There were significant cortisol responses to all treatments at both ages. Sex differences in the cortisol responses to tail docking and ACTH developed between 1 and 8 weeks of age, with females having greater responses than males. The data suggest that the mechanism for the sex difference in response to tail docking may involve the adrenal glands. At both ages, in males, the cortisol response to the combined treatment of tail docking and castration was significantly greater than that for tail docking alone.

Adrenal Glands↗

PubMed2006

Stress, cortisol and reproduction in female pigs.

Two key hypotheses emerge in the literature regarding the impact of stress on reproduction in females of any species. First, prolonged stress impairs reproduction in females. Secondly, acute stress impairs reproduction, if it occurs at a critical time during the precisely timed series of endocrine events that induce oestrus and ovulation. We reviewed studies conducted in female pigs to find support or opposition for these hypotheses in female pigs. We also considered the role of cortisol. We found confirmation that prolonged stress or the prolonged elevation of cortisol can impair reproductive processes in female pigs, but also found that there appear to be some female pigs in which reproduction is resistant to such treatments. Reproduction in female pigs appears to be resistant to acute or repeated acute stress or elevation of cortisol, even if these occur during the series of precisely timed endocrine events that induce oestrus and ovulation. Thus, we propose modified versions of the above hypotheses that are specific to female pigs. Furthermore, while cortisol may mediate the effects of prolonged stress on reproduction in female pigs, there is evidence that, in female pigs, ACTH may require the presence of the adrenal glands to impair reproduction rather than having direct effects.

Adrenal Glands↗

PubMed2005

Susceptibility of reproduction in female pigs to impairment by stress or elevation of cortisol.

It is generally agreed that stress can impair reproduction. Furthermore, it is often thought that cortisol, which is secreted during stress as a result of activation of the hypothalamo-pituitary adrenal axis, is associated with this stress-induced impairment of reproduction. It has been hypothesized that reproduction in females is particularly susceptible to disruption by acute stress during the series of endocrine events that induce estrus and ovulation. Nevertheless, we found no support for this conjecture when we subjected female pigs to repeated acute stress or repeated acute elevation of cortisol during the period leading up to estrus and ovulation. Conversely, studies have demonstrated that prolonged stress and sustained elevation of cortisol can disrupt reproductive processes in female pigs. Nevertheless, in each study that demonstrated this effect, there were some animals subjected to the prolonged stressor or the sustained elevation of cortisol in which the reproductive parameters that were measured were not affected by the treatment. We propose that reproduction in female pigs is resistant to the effects of acute or repeated acute stress or acute or repeated acute elevation of cortisol even if these occur during the series of endocrine events that induce estrus and ovulation. Furthermore, while reproductive processes in some individuals are compromised, reproduction in a proportion of female pigs appears to be resistant to the effects of prolonged stress or sustained elevation of cortisol.

Animals↗

PubMed2005

Co-localization and distribution of corticotrophin-releasing hormone, arginine vasopressin and enkephalin in the paraventricular nucleus of sheep: a sex comparison.

The paraventricular nucleus (PVN) is integral to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and contains cells producing corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and enkephalin. We used immunohistochemistry to map these peptides and to resolve the extent of co-localization within PVN cells in intact and gonadectomized male and female sheep. Immunoreactive (ir) CRH, AVP and enkephalin cells were mapped in two rams and two ewes at 180 mum intervals throughout the rostro-caudal extent of the PVN. Similar distributions of AVP-ir cells occurred in both sexes whereas CRH-ir and enkephalin-ir cells extended more rostrally in rams. In groups (n=4) of intact and gonadectomized sheep of both sexes, co-localization and distribution of neuropeptides was influenced by sex and gonadectomy. Males had more AVP and CRH cells than females. Intact animals had more AVP cells than gonadectomized animals. There were no differences between groups in the number or percentage of cells that stained for both CRH and AVP or in the number of cells that stained for both CRH and enkephalin. Differences were observed in the percentage of enkephalin cells that contained CRH with males having a greater percentage of co-localized cells than did females. Differences were also observed in the number and percentage of cells that stained for both enkephalin and AVP; the number of cells that stained for both neuropeptides was greater in males than in females and greater in intact animals than in gonadectomized animals. Differences were observed in the percentage of AVP cells that contained enkephalin, and in the percentage of enkephalin cells that contained AVP with males having a greater percentage of co-localized cells than did females. We conclude that sex and gonadal status affect peptide distribution in the PVN of the sheep which may provide an anatomical basis for sex differences in HPA axis responses to stress.

Animals↗

PubMed2004

Reconstruction of in vivo time-evolving neuroendocrine dose-response properties unveils admixed deterministic and stochastic elements.

Homeostasis in the intact organism is achieved implicitly by repeated incremental feedback (inhibitory) and feedforward (stimulatory) adjustments enforced via intermittent signal exchange. In separated systems, neurohormone signals act deterministically on target cells via quantifiable effector-response functions. On the other hand, in vivo interglandular signaling dynamics have not been estimable to date. Indeed, experimentally isolating components of an interactive network definitionally disrupts time-sensitive linkages. We implement and validate analytical reconstruction of endogenous effector-response properties via a composite model comprising (i) a deterministic basic feedback and feedforward ensemble structure; (ii) judicious statistical allowance for possible stochastic variability in individual biologically interpretable dose-response properties; and (iii) the sole data requirement of serially observed concentrations of a paired signal (input) and response (output). Application of this analytical strategy to a prototypical neuroendocrine axis in the conscious uninjected horse, sheep, and human (i) illustrates probabilistic estimation of endogenous effector dose-response properties; and (ii) unmasks statistically vivid (2- to 5-fold) random fluctuations in inferred target-gland responsivity within any given pulse train. In conclusion, balanced mathematical formalism allows one to (i) reconstruct deterministic properties of interglandular signaling in the intact mammal and (ii) quantify apparent signal-response variability over short time scales in vivo. The present proof-of-principle experiments introduce a previously undescribed means to estimate time-evolving signal-response relationships without isotope infusion or pathway disruption.

Animals↗

PubMed2004

Leptin-mediated effects of undernutrition or fasting on luteinizing hormone and growth hormone secretion in ovariectomized ewes depend on the duration of metabolic perturbation.

We aimed to determine the importance of leptin in the regulation of luteinizing hormone (LH) and growth hormone (GH) secretion in ovariectomized (OVX) ewes. Lean and fat sheep were produced by dietary manipulation over 8 months and were then fasted for 32 h. Plasma concentrations of glucose, insulin and leptin were higher in the fat group. Fasting decreased plasma concentrations of glucose and insulin and increased concentrations of nonesterified fatty acids (NEFA) in fat and lean ewes, but leptin concentrations were reduced in the fat group only. Plasma GH concentrations were higher in the lean group and LH concentrations were lower; there was no effect of fasting. These data suggested that long-term changes in plasma leptin concentrations might affect LH and GH secretion, but acute changes with fasting had no effect. OVX ewes of normal body weight were fasted for 72 h with or without intracerebroventricular (i.c.v.) infusion of leptin (4 microg/h), achieving similar metabolic effects to the 32 h fast. The 72-h fast increased LH pulse amplitude, mean GH and cortisol concentrations, but these changes were corrected towards normal by leptin treatment. Thus, leptin could attenuate fasting-induced alterations in the secretion of LH, GH and cortisol. Finally, we food-restricted OVX ewes for 4 months (lean), leading to a 20-kg reduction in body weight. Plasma concentrations of leptin and insulin were decreased, and plasma GH concentrations increased, but there was no effect on plasma concentrations of LH, glucose or NEFA. Icv infusion of leptin did not affect any endocrine or metabolic parameter in these ewes. In summary, maintenance of a lean or fat condition for a prolonged period (8 months) or an extended fasting (72 h) can affect LH and GH secretion, but short-term food restriction (4 months) affected only GH secretion and short-term fasting (32 h) had no effect on either LH or GH secretion. This is in spite of altered plasma leptin concentrations in all circumstances studied. Although leptin treatment can restore plasma concentrations of LH, GH and cortisol towards normal in sheep fasted for 72 h, some other factor(s) must signal to the brain to cause shifts in neuroendocrine function in other conditions where nutritional/metabolic status is altered.

Animals↗

PubMed2004

Sex differences in the distribution and abundance of androgen receptor mRNA-containing cells in the preoptic area and hypothalamus of the ram and ewe.

Rams and ewes show a negative-feedback response to peripheral treatment with testosterone, with both sexes having a similar degree of suppression in luteinizing hormone (LH) secretion during the breeding season. At least part of the action of testosterone to suppress gonadotropin-releasing hormone/LH secretion is exerted via interaction with an androgen receptor. The distribution of androgen receptor-containing cells in the hypothalamus has been described for the ram, but similar studies have not been performed in the ewe. In the present study, we tested the hypothesis that levels of androgen receptor mRNA expression in the preoptic area and hypothalamus would be similar in rams and ewes. Perfusion-fixed brain tissue was obtained from adult Romney Marsh ewes (luteal phase) and rams during the breeding season (n = 4/sex). Androgen receptor mRNA expression was quantified in hypothalamic sections by in situ hybridization using an (35)S-labelled riboprobe and image analysis. Hybridizing cells were found in the medial preoptic area, bed nucleus of the stria terminalis, anterior hypothalamic area, ventromedial nucleus, arcuate nucleus and premamillary nucleus. The level of androgen receptor mRNA expression was higher in rams than ewes in the rostral preoptic area, caudal preoptic area and rostral portion of the bed nucleus of the stria terminalis, with no sex difference in other regions. The preoptic area and bed nucleus of the stria terminalis are important for reproductive behaviour and the sex differences in androgen receptor mRNA expression at these levels may relate to this. The high level of androgen receptor mRNA expression in the basal hypothalamus, with no sex difference, is consistent with the role of this region in the regulation of gonadotropin secretion.

Animals↗

PubMed2003

Seasonal differences in the effect of isolation and restraint stress on the luteinizing hormone response to gonadotropin-releasing hormone in hypothalamopituitary disconnected, gonadectomized rams and ewes.

Stress responses are thought to act within the hypothalamopituitary unit to impair the reproductive system, and the sites of action may differ between sexes. The effect of isolation and restraint stress on pituitary responsiveness to GnRH in sheep was investigated, with emphasis on possible sex differences. Experiments were conducted during the breeding season and the nonbreeding season. In both experiments, 125 ng of GnRH was injected i.v. every 2 h into hypothalamopituitary disconnected, gonadectomized rams and ewes on 3 experimental days, with each day divided into two periods. During the second period on Day 2, isolation and restraint stress was imposed for 5.5 h. Plasma concentrations of LH and cortisol were measured in samples of blood collected from the jugular vein. In the second experiment (nonbreeding season), plasma concentrations of epinephrine, norepinephrine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylglycol were also measured. In both experiments, there was no effect of isolation and restraint stress on plasma concentrations of cortisol in either sex. During the breeding season, there was no effect of isolation and restraint stress on plasma concentrations of LH in either sex. During the nonbreeding season, the amplitude of the first LH pulse after the commencement of stress was significantly reduced (P < 0.05) in rams and ewes. In the second experiment, during stress there was a significant increase (P < 0.05) in plasma concentrations of epinephrine in rams and ewes and significantly higher (P < 0.05) basal concentrations of norepinephrine in ewes than in rams. These results suggest that in sheep stress reduces responsiveness of the pituitary gland to exogenous GnRH during the nonbreeding season but not during the breeding season, possibly because of mediators of the stress response other than those of the hypothalamus-pituitary-adrenal gland axis.

Animals↗

PubMed2003

Neuropeptide Y (NPY) delays the oestrogen-induced luteinizing hormone (LH) surge in the ovariectomized ewe: further evidence that NPY has a predominant negative effect on LH secretion in the ewe.

Studies in rats suggest that neuropeptide Y (NPY) plays a stimulatory role in the generation of the preovulatory luteinizing hormone (LH) surge, via the Y1 receptor. We have investigated this issue using the oestradiol benzoate (EB)-treated ovariectomized (OVX) ewe which is a model for the preovulatory LH surge. A Y1 receptor antagonist (BIBO3304) was infused (25 microg/h) into the third cerebral ventricle (III-V) from 2 h before EB injection for 24 h, and had no effect on the ensuing LH surge. Using in situ hybridization, we then examined expression of NPY mRNA in the arcuate nucleus during the luteal, follicular and oestrous phases of the oestrous cycle, and found that levels were greatest during the luteal phase. Thus, reduced NPY synthesis might be an integral factor in the events leading to the cyclic preovulatory LH surge. This was tested by infusion of NPY (25 microg/h) into the III-V (as above). The NPY infusion delayed the LH surge until the infusion was ceased. High levels of NPY expression during the luteal phase of the oestrous cycle may be caused by progesterone. Thus, we determined whether NPY cells possess progesterone receptors (PR) and whether progesterone treatment up-regulates NPY mRNA expression in the arcuate nucleus. Immunohistochemistry for NPY and PR was performed in OVX, oestrogen-treated ewes, but no NPY cells of the arcuate nucleus were seen to colocalize PR. In situ hybridization for NPY was performed in OVX and OVX ewes treated with progesterone. There was no significant effect of progesterone treatment on NPY mRNA expression in the arcuate nucleus. We conclude that chronically elevated levels of NPY block the preovulatory surge of gonadotropin-releasing hormone/LH secretion in sheep, but high levels of NPY mRNA expression in the luteal phase of the oestrous cycle cannot be explained by an action of progesterone.

Animals↗

PubMed2002

Stress and reproduction: central mechanisms and sex differences in non-rodent species.

Despite extensive research, the mechanisms by which stress affects reproduction are unknown. Activation of stress systems could potentially influence reproduction at any level of the hypothalamo-pituitary gonadal axis. Nonetheless, the predominant impact is on the secretion of gonadotrophin releasing hormone (GnRH) from the brain and the secretion of the gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), from the gonadotrophs of the anterior pituitary gland. When stress is prolonged, it is likely that secretion of the gonadotrophins will be suppressed but the effects of acute stress or repeated acute stress are not clear. Different stressors activate different pathways for varying durations, and the actions of stress vary with sex and are influenced by the predominance of particular sex steroids in the circulation. The mechanisms by which stress influences reproduction are likely to involve complex interactions between a number of central and peripheral pathways and may be different in males and females. To understand these mechanisms, it is important to determine the stress pathways that are activated by particular stressors and to establish how these pathways affect the secretion and actions of GnRH. Furthermore, there is a need to know how stress influences the feedback actions of gonadal steroids and inhibin.

Animals↗

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

Differential expression of cocaine- and amphetamine-regulated transcript and agouti related-protein in chronically food-restricted sheep.

Recently, much attention has focused on the role of the melanocortin system in the regulation of energy homeostasis, especially the satiety effects of the pro-opiomelanocortin (POMC)-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH). We have found that POMC mRNA levels are similar in fat and thin sheep and the current study sought to further characterize the effects of nutritional status on the melanocortin system. To this end, we studied the expression of agouti-related peptide (AGRP) (an endogenous antagonist of alpha-MSH) and cocaine- and amphetamine-regulated transcript (CART), which is co-localized within POMC cells of the arcuate nucleus (ARC) in rodents. Twelve ovariectomized ewes were randomly divided into two groups and fed a maintenance (n=6) or restricted diet (n=6). At the time of experimentation, the animals had significantly (P<0.0001) different bodyweights (53.4+/-2.2 kg, ad libitum vs. 30.4+/-1.2 kg, food-restricted), which was largely due to altered body fat deposits. In situ hybridization was used to study the expression of POMC, AGRP and CART. The expression of POMC in the ARC was similar in ad libitum and food-restricted animals but the expression of AGRP was profoundly increased in the food-restricted group. The expression of CART was abundant throughout the hypothalamus but was not found in the ARC. In food-restricted animals, the expression of CART was lower in the retrochiasmatic nucleus (P<0.01), paraventricular nucleus (P<0.001), the dorsomedial nucleus and the lateral hypothalamic area (P<0.05), but was higher (P<0.01) in the posterior hypothalamic area. Thus, long-term changes in nutritional status have profound effects on the expression of AGRP and CART in the hypothalamus.

Agouti-Related Protein↗

PubMed2001

Changes in preoptic and hypothalamic levels of progesterone receptor mRNA across the oestrous cycle of the ewe.

We measured the levels of progesterone receptor (PR) mRNA in the hypothalamus and preoptic area (POA) of the ewe across the oestrous cycle. Perfusion-fixed hypothalamic tissue was collected from sheep killed during the luteal and follicular phases and during behavioural oestrus. Blood samples taken at the time of tissue collection verified that the oestrous ewes were undergoing a preovulatory luteinizing hormone (LH) surge. Matched sections were taken from the POA, periventricular nucleus (PeVN), ventromedial nucleus (VMN) and arcuate nucleus of each animal. In situ hybridization was performed using a sheep specific, (35)S-labelled riboprobe for PR and semiquantitative image analysis was conducted on emulsion-dipped slides. The number of silver grains per cell was greater in the VMN and arcuate nucleus of oestrous ewes than in luteal and follicular phase ewes; there was no cyclic variation in the level of PR mRNA expression in the cells of the POA and PeVN. The number of labelled cells per mm2 in the VMN was higher in the oestrous ewes than in luteal phase and follicular phase ewes. The number of labelled cells in the PeVN was also higher in the oestrous ewes than in follicular phase ewes, but there was no cyclic variation in the POA and arcuate nucleus. In the ewe, the onset of behavioural oestrus corresponds to the onset of the preovulatory LH surge and increased PR mRNA expression at this time is likely to be due to the high concentrations of circulating oestrogen that precede this period.

Animals↗

PubMed2001

Influence of the degree of stimulation of the pituitary by gonadotropin-releasing hormone on the action of inhibin and testosterone to suppress the secretion of the gonadotropins in rams.

This experiment determined if the degree of stimulation of the pituitary gland by GnRH affects the suppressive actions of inhibin and testosterone on gonadotropin secretion in rams. Two groups (n = 5) of castrated adult rams underwent hypothalamopituitary disconnection and were given two i.v. injections of vehicle or 0.64 microg/kg of recombinant human inhibin A (rh-inhibin) 6 h apart when treated with i.m. injections of oil and testosterone propionate every 12 h for at least 7 days. Each treatment was administered when the rams were infused i.v. with 125 ng of GnRH every 4 h (i.e., slow-pulse frequency) and 125 ng of GnRH every hour (i.e., fast-pulse frequency). The FSH concentrations and LH pulse amplitude were lower and the LH concentrations higher during the fast GnRH pulse frequency. The GnRH pulse frequency did not influence the ability of rh-inhibin and testosterone to suppress FSH secretion. Testosterone did not affect LH secretion. Following rh-inhibin treatment, LH pulse amplitude decreased at the slow, but not at the fast, GnRH pulse frequency, and LH concentrations decreased at both GnRH pulse frequencies. We conclude that the degree of stimulation of the pituitary by GnRH does not influence the ability of inhibin or testosterone to suppress FSH secretion in rams. Inhibin may be capable of suppressing LH secretion under conditions of low GnRH.

Animals↗

PubMed2001

Negative feedback regulation of the secretion and actions of gonadotropin-releasing hormone in males.

This minireview considers the state of knowledge regarding the interactions of testicular hormones to regulate the secretion and actions of GnRH in males, with special focus on research conducted in rams and male rhesus monkeys. In these two species, LH secretion is under the negative feedback regulation of testicular steroids that act predominantly within the central nervous system to suppress GnRH secretion. The extent to which these actions of testicular steroids result from the direct actions of testosterone or its primary metabolites, estradiol or dihydrotestosterone, is unclear. Because GnRH neurons do not contain steroid receptors, the testicular steroids must influence GnRH neurons via afferent neurons, which are largely undefined. The feedback regulation of FSH is controlled by inhibin acting directly at the pituitary gland. In male rhesus monkeys, the feedback regulation of FSH secretion is accounted for totally by the physiologically relevant form of inhibin, which appears to be inhibin B. In rams, the feedback regulation of FSH secretion involves the actions of inhibin and testosterone and interactions between these hormones, but the physiologically relevant form of inhibin has not been determined. The mechanisms of action for inhibin are not known.

Animals↗

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↗