The influence of 17beta-oestradiol on corticotrophin-releasing hormone induced suppression of luteinising hormone pulses and the role of CRH in hypoglycaemic stress-induced suppression of pulsatile LH secretion in the female rat

Corticotrophin-releasing hormone (CRH) released during stress has been implicated in the disruption of the reproductive neuroendocrine axis, and 17beta-oestradiol (E2) has been shown to enhance stress-induced suppression of pulsatile gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) release. The aims of the present study were to examine the role of CRH in hypoglycaemic stress-induced suppression of LH pulses, and to investigate the influence of E2 on the inhibitory effect of CRH on pulsatile LH secretion in the female rat. Suppression of LH pulses by insulin-induced hypoglycaemic (IIH) stress was completely prevented by intracerebroventricular (icv) administration of a CRH antagonist. Central administration of CRH (5 microg) resulted in an interruption of LH pulses in E2 treated animals, but had little or no effect in the absence of this gonadal steroid. These results provide evidence of a pivotal role for CRH in mediating the suppressive effect of IIH stress on pulsatile LH secretion in the female rat, and highlight a sensitising role for E2 in CRH-induced suppression of LH pulses.     

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.     

Hypoglycemia-induced suppression of luteinizing hormone (LH) secretion in intact female rhesus macaques: role of vasopressin and endogenous opioids

The first objective of this study was to determine whether insulin-induced hypoglycemia (IIH) inhibits LH secretion in unrestrained female macaques during the follicular phase of the menstrual cycle. There was a consistent inhibitory effect of hypoglycemia on LH secretion within 3 h in these females. This inhibition was likely an indirect effect since low glucose levels did not inhibit GnRH secretion from GT1-1 neurones in vitro. We next investigated whether administration of a vasopressin antagonist (AVPa) either alone, or with naloxone could reverse the IIH-induced inhibition of LH release. Females were studied in the follicular phase during 10 h periods with blood samples collected every 10 min. Experimental groups were IIH (n=6), IIH+AVPa (n=5) and IIH+AVPa+naloxone (n=4). The first 5 h of each study served as a control and hypoglycemia was then induced with insulin. The AVPa was given as a bolus (180 microg) just before the insulin and was followed by a continuous infusion (180 microg/h) for 5 h. Naloxone (5 mg/kg) was given with the AVPa and followed by a continuous infusion (5 mg/kg/h) for 5 h. In the IIH group, LH reached its lowest value 3-4 h after insulin. Neither AVPa nor AVPa+naloxone infusion reversed the inhibitory action of hypoglycemia on LH release. These data suggest that if there are inhibitory actions of vasopressin and endogenous opioids on GnRH release induced by hypoglycemia, they are not sufficient to explain the suppression of GnRH/LH release in intact female primates.     

Neuroendocrine responses to psychological stress in eumenorrheic and oligomenorrheic women

Neuroendocrine adaptive responses to psychological stress include activation of the hypothalamic-pituitary-adrenal (HPA) axis and sometimes suppression of the hypothalamic-pituitary-gonadal (HPG) axis. In women who experience chronic stress, these responses are probably responsible for disturbances in the menstrual cycle. In the present experiment, we investigated the effect of an acutely stressful situation on the physiological and neuroendocrine responses in college age women. We hypothesized that females who are experiencing some degree of abnormal menstrual function or women who have less-robust cycles (oligomenorrheic females) would exhibit differences in gonadotropin secretion from eumenorrheic females when exposed to psychological stressors. Fifteen women completed this study: eumenorrheic (n = 5) and oligomenorrheic women (n = 5) who experienced a series of psychological stressors, and eumenorrheic controls (n = 5). Blood samples were taken at 10 min intervals for 8 h (09:00-17:00) in each woman during the mid-follicular phase of the menstrual cycle. The psychological stressors were administered for 1 h beginning at 13:00 h. Luteinizing hormone (LH), growth hormone (GH) and cortisol were measured in each sample to assess the effect of stress on secretion of these hormones. Deconvolution analysis was used to analyze pulsatile hormone secretion and the approximate entropy (ApEn) statistic analyzed the regularity of release of each hormone. Although, there were significant changes in heart rate (HR), skin resistance (SR) and cortisol levels in the stressed women during the psychological stressor compared to resting baseline values but not in the controls, there was no difference in either LH or GH secretion between women who experienced stress and those who did not. Furthermore, there were no differences in the LH or GH secretion patterns in the oligomenorrheic and eumenorrheic women exposed to the psychological stressor.     

Chronic psychological stress and the regulation of pro-inflammatory cytokines: a glucocorticoid-resistance model.

This study examined whether chronic stress impairs the immune system's capacity to respond to hormonal signals that terminate inflammation. Fifty healthy adults were studied; half were parents of cancer patients, and half were parents of healthy children. Parents of cancer patients reported more psychological distress than parents of healthy children. They also had flatter diurnal slopes of cortisol secretion, primarily because of reduced output during the morning hours. There was also evidence that chronic stress impaired the immune system's response to anti-inflammatory signals: The capacity of a synthetic glucocorticoid hormone to suppress in vitro production of the pro-inflammatory cytokine interleukin-6 was diminished among parents of cancer patients. Findings suggest a novel pathway by which chronic stress might alter the course of inflammatory disease.     

The role of corticotrophin-releasing hormone receptors in the calcitonin gene-related peptide-induced suppression of pulsatile luteinising hormone secretion in the female rat

Corticotrophin-releasing hormone (CRH) plays a pivotal role in the suppression of the gonadotrophin-releasing hormone (GRH) pulse generator in response to stress and intracerebroventricular (i.c.v.) administration of calcitonin gene-related peptide (CGRP). We have previously shown both CRH receptor subtypes, CRH-R1 and CRH-R2, are involved in the stress-induced suppression of LH pulses. The aims of the present study were to examine the role of CRH-R1 and CRH-R2 in CGRP-induced suppression of LH pulses, and to investigate the effects of CGRP on CRH expression in the paraventricular nucleus (PVN) and central nucleus of the amygdala (CeA), which have prominent CRH neurone populations that receive dense CGRP innervations. The suppression of LH pulses by CGRP (1.5 microg i.c.v.) was completely prevented by intravenous administration of the CRH-R1 antagonist SSR125543Q (7.5 mg/rat i.v., 30 min before CGRP), but was not affected by the CRH-R2 antagonist, astressin(2)-B (100 microg i.c.v., 10 min before CGRP). CGRP increased the CRH mRNA expression in PVN and CeA. These results provide evidence of a role for CRH-R1 in mediating the suppressive effects of CGRP on pulsatile LH secretion in the female rat, and additionally raise the possibility of an involvement of PVN and CeA CRH neuronal populations in this suppression.     

The Left Hand Doesn't Know What the Right Hand Is Doing: The Disruptive Effects of Attention to the Hands in Skilled Typewriting

ABSTRACT— Everyone knows that attention to the details disrupts skilled performance, but little empirical evidence documents this fact. We show that attention to the hands disrupts skilled typewriting. We had skilled typists type words preceded by cues that told them to type only the letters assigned to one hand or to type all of the letters. Cuing the hands disrupted performance markedly, slowing typing and increasing the error rate (Experiment 1); these deleterious effects were observed even when no keystrokes were actually inhibited (Experiment 3). However, cuing the same letters with colors was not disruptive (Experiment 2). We account for the disruption with a hierarchical control model, in which an inner loop controls the hands and an outer loop controls what is typed. Typing letters using only one hand requires the outer loop to monitor the inner loop's output; the outer loop slows inner-loop cycle time to increase the likelihood of inhibiting responses with the unwanted hand. This produces the disruption.     

Cytokine production by spleen cells after social defeat in mice: activation of T cells and reduced inhibition by glucocorticoids

Social disruption (SDR) is an effective model of social stress associated with an enhanced inflammatory reactivity of the immune system. The aim of the present study was to further describe SDR effects on cytokine production by spleen cells, testing selectively monocyte and T cell functions as a result of this stressor. For this purpose, splenocytes from control mice (C) and mice socially stressed for 7 days (SDR) were cultured in the presence of lipopolysaccharide (LPS) or concanavalin A (Con A). Splenocyte proliferation, cytokine production and sensitivity of spleen cells to corticosterone were assessed in vitro. The humoral response to keyhole limpet hemocyanin (KLH) immunization was assessed. SDR induced splenomegaly and enhanced splenocyte basal proliferation. The pro-inflammatory influence of SDR was confirmed by an increased release of interleukin-6 (IL-6) by LPS-stimulated cultures and by a reduced sensitivity of spleen cells to the anti-inflammatory effect of corticosterone. The mechanism increasing cytokine production in response to LPS was cytokine specific, since among inflammatory cytokines, IL-6 but not interferon-gamma (IFN-gamma) was enhanced by stress. In stressed mice, the increase in IL-6 and IFN-gamma and the decrease in IL-10 release in Con A-stimulated cultures indicate that SDR did not modify the Th1/Th2 cytokine balance but globally activated T cells. Plasma anti-KLH antibody levels were similar in both groups. Wounded and non-wounded mice presented similar responses to stress. This study shows that social disruption stress enhances the reactivity of cells from both the acquired and innate immune systems.     

Gastric mucosal damage induced by lateral hypothalamic lesions in female rats: influence of age and ovariectomy

Male rats given lateral hypothalamic (LH) lesions exhibit an acute increase in gastric acid secretion and develop erosions of the glandular portion of the stomach within 24 h. Since this process has been examined predominantly in male rats, the present experiments were devised to study the effects of LH lesions on the gastric mucosa of female rats. In Experiment 1, 1-year-old Sprague-Dawley female rats given LH lesions exhibited erosions in the rumenal portion of the stomach, a pattern unlike that found in both young and old male rats. Although the glandular mucosa lacked evidence of gross defects, the mucosa appeared blanched and covered with a mucus-like secretion. Experiment 2 demonstrated that, like male rats, LH lesions produced gastric hypersecretion in 1-year-old females. The results of the first two experiments indicate that the dissimilar patterns of gastric mucosal injury between males and older females cannot be accounted for on the basis of differences in gastric acid secretion. Experiment 3 demonstrated that, unlike older females but like males, 4-month-old female rats given LH lesions developed gastric erosions in the glandular mucosa only. Additionally, ovariectomy had no significant effect in altering the extent of gastric pathology. Taken together, these results suggests that (1) age and gender are important variables in neurogenic gastric mucosal injury, (2) differences in the type of gastric ulceration cannot be accounted for by differences in acid secretion, (3) ovarian hormones do not appear to play a significant role in gastric ulceration following brain damage.     

Does IL-6 release ACTH by exerting a direct effect in the rat anterior pituitary

Adult male rats were used to determine whether high circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) were capable of releasing ACTH independently of endogenous corticotropin-releasing factor (CRF). On one hand, CRF antibodies or a potent CRF antagonist significantly decreased, but did not totally abolish the ACTH response to the intravenous(i.v.) injection of recombinant rat IL-6. These results suggest that this cytokine might act either directly on the pituitary, or can release ACTH through mechanisms that do not involve CRF. On the other hand, the CRF antagonist or antibodies significantly (but not totally) blocked ACTH secretion due to the i.v. injection of endotoxin (LPS) while enhancing the ability of this immune stimulus to increase serum IL-6 concentrations. These results indicate that during endotoxemia, even very elevated circulating IL-6 concentrations were notable to release large amounts of ACTH in the absence of CRF drive. These data also illustrate the ability of a CRF antagonist or CRF antibodies to significantly augment IL-6 secretion,which indicates an inhibitory influence of the endogenous peptide in the paradigm we used.As comparable findings were obtained in adrenal-intact and adrenalectomized rats, they suggest that endogenous CRF is involved in the IL-6 response to LPS independently of circulating corticosteroids or other adrenal factors.     

Irrelevant Sound Disrupts Order Information in Free Recall as in Serial Recall

The claim that the sensitivity of free recall to disruption by irrelevant sound is a function of the extent to which rote rehearsal is employed as a mnemonic strategy was investigated in two experiments. The degree of disruption by irrelevant sound in terms of both item and order information was contrasted under serial and free recall instructions. Irrelevant sound was found to disrupt order and item information equally in serial and free recall tasks (Experiment 1). Contrary to previous reports, an effect of irrelevant sound was also demonstrated on free recall of particularly long lists, and the interaction between list length and retention interval in the irrelevant sound effect was examined (Experiment 2). Generally, the results support the view that irrelevant sound disrupts the use of order cues.     

Word Dose in the Disruption of Serial Recall by Irrelevant Speech: Phonological Confusions or Changing State?

Irrelevant background speech disrupts serial recall of visually presented lists of verbal material. Three experiments tested the hypothesis that the degree of disruption is dependent on the number of words heard (i.e. word dose) whilst the task was undertaken. Experiments 1 and 2 showed that more disruption is produced if the word dose is increased, thereby providing evidence to support the experimental hypothesis. It was concluded from the first two experiments that the word-dose effect might be the result of increasing the amount of changing-state information in the speech. The results of Experiment 3 supported this conclusion by showing an interaction between word dose and changing-state information. It was noted however that the results might be explained within the working memory account of the disruptive action of irrelevant speech. A further two experiments cast doubt on this possibility by failing to replicate the finding that the phonological similarity between heard and seen material affects the degree of interference (Salame & Baddeley, 1982). The findings are discussed in relation to the changing state hypothesis of the irrelevant speech effect (e.g. Jones, Madden, & Miles, 1992).     

Immune responses to lipopolysaccharide challenge in a tropical rodent (Funambulus pennanti): photoperiod entrainment and sex differences

Annual variation in day length (photoperiod) triggers changes in the immune system of seasonal breeders. The rationale behind this study was to delineate any sex differences in immune responses of photoperiodically entrained animals challenged against lipopolysaccharide (LPS)-induced inflammatory stress. We observed that photoperiodically entrained [short day, SD, 10?h light (L):14?h dark (D); long day, LD, 16?h L:8?h D; and natural day length, NDL, 12?h L:12?h D] male and female Indian palm squirrels, Funambulus pennanti, presented sexual dimorphism in immune status after LPS-induced stress. Females presented high humoral (anti-keyhole limpet hemocyanin immunoglobulin) and cellular immunity (lymphocyte proliferation) compared with the males of all photoperiodic conditions. Female squirrels showed reduced pro-inflammatory cytokine levels (interleukin-1β, interleukin-6, and tumor necrosis factor-α) than the males suggesting their high efficiency to recover from LPS-induced inflammatory stress. Increased duration of melatonin secretion and corticosterone concentration in squirrels experiencing SD evidently supported survival of squirrels as compared with control (NDL) and LD squirrels of both sexes. Decreased immune status in both sexes under LD condition might be due to a short melatonin signal mimicking the LDs of summer. Thus, we infer that photoperiodic entrainment via the levels of melatonin and corticosterone synergistically supported more the survival of female squirrels under LPS-induced stress.     

Crowding-induced changes in basal and stress levels of thyrotropin and somatotropin in male rats

The effects of crowding on thyrotropin (TSH) and somatotropin (GH) secretion were studied in two-month-old male rats. Crowded rats (9-10 per cage) showed lower serum GH levels than controls (3 per cage). Likewise, serum GH was lower in crowded rats after acute exposure to stress. However, percentage inhibition of GH secretion induced by acute stress was similar in crowded and control rats. Crowding reduced the TSH response to acute stress. The results found with the administration of hypothalamic regulatory factors suggest that the impaired GH and TSH secretion observed in crowded rats was not likely to be at the pituitary level. Therefore, altered neuroendocrine control of GH and TSH secretion appears to exist in crowded rats. Preliminary results obtained in rats crowded from weaning to adulthood suggest that food restriction only partially accounts for the changes observed in crowded rats.     

Disruption of short-term memory for reinforcement by ambient illumination

Pigeons were trained on a delayed conditional discrimination (DCD) in which choice of one of two simultaneously presented stimuli was reinforced if the trial had been initiated by presentation of a food sample. On trials in which no sample was presented, choice of the other colour was reinforced. Illumination of the houselights during the retention interval was provided in an attempt to interfere with retention of information about the food sample which served as a conditional cue. In two experiments, retention interval illumination produced a greater disruption of DCD performance on no sample trials than on food sample trials. The finding that retention interval illumination disrupts DCD performance on no sample trials suggests that this manipulation does not affect memorial processes since there was good evidence that performance on no sample trials did not depend on remembering what happened at the outset of the trial. Furthermore, the magnitude of the disruption was larger if the illumination immediately preceded the choice stimuli than if it followed presentation of the sample stimuli. These results support the hypothesis that retention interval illumination disrupts DCD performance by interfering with discriminative control of the choice response rather than with memorial processes. In neither study did retention interval illumination impair discriminative autoshaping to keylight stimuli that immediately preceded the food sample and no sample DCD trials.     

A strategy disruption component to retrieval-induced forgetting

Retrieval-induced forgetting refers to a paradoxical occurrence wherein the act of remembering some material disrupts the retrieval of other, related material (see, e.g., M. C. Anderson, R. A. Bjork, & E. L. Bjork, 1994). This effect is generally accounted for in terms of inhibitory processes. Across three experiments, we test the inhibitory account of retrieval-induced forgetting, as well as whether there may be a strategy disruption component to the effect. In our first two experiments, we manipulate which items individuals are cued to recall during retrieval practice and demonstrate that retrieval-induced forgetting can be neutralized when those items do not interfere with the individual's retrieval strategy. In the third experiment, we confirm this finding with a different set of stimuli. These results are inconsistent with a purely inhibitory account of retrieval-induced forgetting, and we discuss implications for inhibition theory and strategy disruption in light of these and other findings.     

Inhibition of the LH Surge by Restraint Stress in Cyclic Rats: Studies on the Role of GABAA and GABAB Receptors

There is evidence that stress can alter the activity in the brain of gamma-aminobutyricacid (GABA), a neurotransmitter that has been implicated in the regulation of LH secretion. In the present study the role of GABA in the restraint stress-induced inhibition of the LH surge was investigated in the intact cyclic rat. Intracerebroventricular (icv) administration of the GABAA receptor agonist muscimol (0.1, 0.5 or 1 μg) 5 min before the presumed onset of the pro-oestrous LH surge (at 0900 h) caused a dose dependent suppression of the surge. A single dose of the GABAB receptor agonist baclofen (1 μg; icv) injected at 0855 h postponed the onset of the LH surge, and repeated injections at 0855 and 1130 h suppressed the surge. These data indicate that GABA-ergic activity in the brain can inhibit the LH surge in the cyclic rat via GABAA and GABAB receptors. Pro-oestrous rats were subjected to 5 hrs of restraint starting at 0855 h. Pretreatment with the GABAA receptor antagonist bicuculine (1 μg; icv) at 0840, 0940 and 1040 h or pretreatment with the GABAB receptor antagonist phaclofen (10 μg; icv) at 0840 h were ineffective in preventing the restraint-induced inhibition of the LH surge. The results suggest that GABAA and GABAB receptors are not involved in the inhibitory effect of restraint stress on the LH surge.