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Biomedical subjects

E H Mougey

Publications and source records attributed to E H Mougey.

At least 19 recordsLinked to original sources
PubMed1995

Treadmill exercise training and estradiol differentially modulate hypothalamic-pituitary-adrenal cortical responses to acute running and immobilization.

It is generally believed that physical fitness promotes health by attenuating responsiveness to other stressors. The experimental evidence for this belief is limited and does not extend to interactions between the hypothalamic-pituitary-adrenal cortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. We tested the hypothesis that treadmill exercise training would lead to an estrogen-dependent hyporesponsiveness of the HPA axis that would generalize to immobilization stress. Ovariectomized female Sprague-Dawley rats (N = 74) that had been treadmill trained (TT) or sedentary for 6 weeks received intramuscular injections of estradiol benzoate (Eb) or sesame oil on each of 3 days prior to 15 min of acute treadmill running or immobilization. Plasma (adrenocorticotrophin) (ACTH), (corticosterone) (B) and (prolactin) (PRL) were determined from trunk blood by radioimmunoassay and compared in a 2 group (TT vs. sedentary)-by-2 treatment (Eb vs. oil)-by-2 acute stressor (running vs. immobilization) design. Home-cage (HC) animals (N = 24) provided baseline hormone levels. ACTH and B levels were elevated after stressors in animals treated with either Eb or oil compared to HC, but increases in PRL after stressors were dependent on Eb. Treadmill exercise training led to an attenuation of ACTH and prolactin to running, but the attenuation did not generalize to immobilization. In contrast, treadmill exercise training led to a hyperresponsiveness of ACTH. Treadmill training did not modulate prolactin responses to immobilization. The modulating effects of the estradiol treatment are consistent with an interaction of the HPA and HPG axes in response to stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1995

Activity-wheel running attenuates suppression of natural killer cell activity after footshock.

We studied whether voluntary running in an activity wheel moderates splenic natural killer (NK) cell cytotoxicity after footshock. Young (50-day) male Fischer 344 rats were randomly assigned to 1) sedentary (n = 16) or 2) activity-wheel (n = 16) groups that each received controllable or uncontrollable footshock on 2 consecutive days or 3) a sedentary home-cage control group (n = 8). Spleens and trunk blood were collected 30 min after the second footshock session. Cytotoxicity was determined by a standard 4-h 51Cr release assay. Percentages of OX6+ (B), OX8+ [T suppressor/cytotoxic (Ts/c)], W3/25+ (T helper), Thy-1.1 (Pan T cell marker), and 5C6+ (NK) cells were determined by flow cytometry. Plasma adrenocorticotropic hormone, corticosterone, and prolactin concentrations were measured by radioimmunoassay as modulators of NK activity. Percentage of specific lysis after footshock was approximately 52% of control values for sedentary animals compared with approximately 96% of control values for activity-wheel animals. The groups did not differ in percentages of NK or Ts/c cells. We conclude that voluntary activity-wheel running protects against the suppression of splenic NK activity induced by footshock. This protective effect of wheel running is not explained by an elevation in baseline NK activity; increased percentages of splenic NK or Ts/c cells; or plasma levels of adrenocorticotropic hormone, corticosterone, and prolactin.

Adrenocorticotropic Hormone↗
PubMed1995

Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1 alpha.

Recombinant human interleukin-1 alpha (rhIL-1 alpha) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1 alpha in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1 alpha administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1 alpha-induced increase in ACTH levels at the doses used. In fact, the rhIL-1 alpha-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus.

Adrenalectomy↗
PubMed1994

Decreased vasopressin content in parvocellular CRH neurosecretory system of Lewis rats.

Rats possess stress-responsive, vasopressin (VP)-expressing and stress-nonresponsive, VP-deficient subpopulations of parvocellular corticotropin-releasing hormone (CRH) neurosecretory cells. Both subpopulations are activated by bacterial lipopolysaccharide (LPS) and cytokines. Lewis rats exhibit hyporesponsive hypothalamo-pituitary-adrenocortical axes (HPAAs). The Lewis CRH neurosecretory system has been reported to be defective in females and normal in males. We used post-embedding electron microscopic (EM) immunocytochemistry to study baseline levels and LPS-stimulated depletion of neurosecretory vesicles. Male Lewis rats possessed normal numbers of CRH+/VP- varicosities and low numbers of CRH+/VP+ varicosities, indicating abnormally low release of VP into portal blood. This defect contrasts with the reported increase in VP content and release in magnocellular neurosecretory cells in Lewis rats.

Animals↗
PubMed1994

Systemically administered histamine H1 and H2 receptor antagonists do not block the ACTH response to bacterial lipopolysaccharide and interleukin-1.

The administration of lipopolysaccharide (LPS) results in the activation of the hypothalamic-pituitary-adrenal axis (HPAA). We recently reported that the participation and interaction of LPS-induced proinflammatory cytokines were obligatory for the stimulation of adrenocorticotropic hormone (ACTH) release by LPS. LPS and LPS-derived cytokines also stimulate the release of histamine (HA). HA is a known hypothalamic neurotransmitter and activates the HPAA. Therefore, to elucidate the role of HA in LPS- and cytokine-induced ACTH release, we evaluated the effects of several HA H1 and H2 receptor antagonists on the ACTH response to LPS, recombinant human interleukin-1 alpha (rhIL-1 alpha) and HA in mice. Although all 3 of the H1 receptor antagonists administered (mepyramine (MEP), diphenhydramine (DPH) or promethazine (PMZ) were able to block the 10-min ACTH response to HA, only PMZ (a less selective H1 receptor antagonist than MEP) was able to reduce the LPS- or rhIL-1 alpha-induced ACTH responses. Ranitidine, a powerful and selective H2 receptor antagonist, had little effect on the LPS- and rhIL-1 alpha-induced ACTH responses, while metiamide (MET), a much less potent first-generation H2 receptor antagonist, substantially diminished ACTH release. The greater effectiveness of PMZ, in contrast to MEP or DPH, probably relates to the ability of phenothiazine derivatives to inhibit non-HA-dependent pathways involved in the stimulation of the HPAA by cytokines; the same may be true of MET.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Synergistic roles of interleukin-6, interleukin-1, and tumor necrosis factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo.

Administration of lipopolysaccharide (LPS) results in activation of the hypothalamic-pituitary-adrenal axis. LPS induces the release of a number of proinflammatory cytokines, i.e. interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF), which activate the hypothalamic-pituitary-adrenal axis as well and may mediate the effects of LPS. Variations in the kinetics of appearance of IL-1, TNF, and IL-6 after LPS challenge suggested that these cytokines may play different roles at different times. To elucidate the mutual dependence and contribution of individual cytokines in the course of LPS-induced ACTH release, we used blocking antibodies to IL-6, TNF, and the IL-1 receptor. Our results demonstrate that anti-IL-6 antibody abrogated ACTH induction throughout the course of the response both 2 and 4 h after LPS challenge. In contrast, anti-IL-1 receptor and anti-TNF antibody, given individually, blocked ACTH production at 4 h, but not at 2 h. Only combined administration of these two antibodies diminished, but did not eliminate, ACTH release at 2 h. This is the first demonstration that all three inflammatory cytokines are obligatory for LPS-induced elevation of plasma ACTH. In addition, these results suggest that IL-1, IL-6, and TNF play different roles in LPS-induced ACTH release.

Adrenocorticotropic Hormone↗
PubMed1992

Hormonal responses to fighting in hamsters: separation of physical and psychological causes.

Male Syrian hamsters were paired and allowed to interact with a conspecific for 15 min a day for 4 days. On the fifth day, the animals were again paired, but they were kept physically separated by a mesh partition that allowed visual, olfactory, and auditory contact between the animals. Controls were placed with conspecifics on each of the 5 testing days, but the partition between them was never removed. Hamsters that were submissive on days 1-4 exhibited elevated plasma adrenocorticotropin-like immunoreactivity (ACTH-LI), beta-endorphin-like immunoreactivity (B-EP-LI), and cortisol on day 5 even though no fighting occurred on that day. Dominant hamsters did not differ from controls. These data support the hypothesis that there is an important psychological component to the pituitary-adrenocortical response in defeated hamsters.

Adrenocorticotropic Hormone↗
PubMed1992

Effects of controllable vs. uncontrollable chronic stress on stress-responsive plasma hormones.

We have previously reported effects of chronic stress on circadian rhythms of temperature, eating, and locomotor activity. These studies were conducted using an around-the-clock signalled intermittent footshock paradigm in which some rats have control over shock termination while other rats are yoked to the rats with control. Although this paradigm is stressful, as suggested by decreases in food intake and disrupted circadian rhythms, rats tolerate the paradigm well, continuing to eat, drink, gain weight, and groom. In the present studies, rats were sacrificed following 3 or 14 days of stress, and plasma was collected for hormonal assays. After 3 days of stress, plasma corticosterone and prolactin levels were elevated in both stress groups compared to controls; yoked rats had higher levels of corticosterone than rats in the group with control over shock termination, while prolactin levels in both stressed groups were similar. ACTH levels were similar in stressed and control rats. After 14 days of stress, ACTH and corticosterone levels in both stress groups were similar to control levels. Prolactin levels were elevated in the yoked experimental group compared to levels in control or controllable stress groups. These data support previous studies suggesting that control over stressors attenuates the effects of stress on physiology and demonstrate that two hormones with diverse biological effects are elevated by chronic stress.

Adrenocorticotropic Hormone↗
PubMed1992

Effects of interleukin-1 on the stress-responsive and -nonresponsive subtypes of corticotropin-releasing hormone neurosecretory axons.

Administration of interleukin-1 (IL-1) induces increases in plasma ACTH and glucocorticoids. Numerous experiments have implicated the hypothalamic CRH neurosecretory system in these responses, but have failed to provide evidence for involvement of the ACTH secretagogue vasopressin (VP). The rat CRH neurosecretory system contains two types of cells: VP expressing and VP deficient. Hence, the above findings suggested that IL-1 may selectively activate the VP-deficient subtype of CRH neurosecretory cells. In this study we employed postembedding electron microscopic immunocytochemistry to directly assay IL-1-induced depletion of secretory vesicles from identified VP-expressing and VP-deficient CRH neurosecretory axons. IL-1-induced depletion of secretory vesicles from these axons was correlated with increases in plasma ACTH and decreases in plasma PRL. No dose of IL-1 was found that could selectively activate one subtype of CRH neurosecretory axons; at doses of 0.67 microgram/100 g and above for both IL-1 alpha and IL-1 beta, equal depletion of vesicles from the two subtypes was observed. Similar results were previously found after the injection of bacterial lipopolysaccharide, which induces the release of IL-1 from macrophages. The findings unequivocally establish for the first time that IL-1 activates hypothalamic CRH neurosecretory cells in the absence of surgical stress, anesthesia, disruption of the infundibular area, or administration of toxic drugs. In addition, these data clearly demonstrate that IL-1 induces the release of VP from neurosecretory axons in the portal capillary zone of the external zone of the median eminence. Previous studies have shown that the VP-deficient subtype of CRH neurosecretory axons is not strongly activated by several types of stress; therefore, activation of the system by inflammatory mediators involves mechanisms different from those mediating the stress response.

Adrenocorticotropic Hormone↗
PubMed1991

Acute and repeated exposure to social conflict in male golden hamsters: increases in plasma POMC-peptides and cortisol and decreases in plasma testosterone.

The purpose of the present study was to characterize the hormonal response of dominant and submissive male hamsters to acute and repeated exposure to social conflict. We found that submissive, but not dominant, males exhibited elevated plasma levels of adrenocorticotropin (ACTH), cortisol, and beta-endorphin (beta-EP) following one exposure to an agonistic encounter. After five exposures to a dominant opponent, submissive males showed smaller, but still significant, elevations in these plasma hormones. After nine exposures, submissive hamsters showed significant elevations only in plasma ACTH and beta-EP. Plasma testosterone was significantly suppressed in submissive males that fought nine times. We conclude that hamsters are a useful species with which to study the neuroendocrine correlates of social behavior.

Adrenocorticotropic Hormone↗
PubMed1991

Interleukin-1 and interleukin-6 act synergistically to stimulate the release of adrenocorticotropic hormone in vivo.

Interleukin-1 (IL-1) and interleukin-6 (IL-6) share a number of biological functions. Because IL-1 induces IL-6 in vivo, the extent to which IL-6 mediates the effects of IL-1 has come under investigation. The stimulation of the hypothalamic-pituitary-adrenal axis by IL-1 and IL-6 is a critical component of the inflammatory response. The present study was designed to compare the effects of recombinant human IL-1 alpha (rhIL-1 alpha) and recombinant human IL-6 (rhIL-6) administered in combination and alone on the release of adrenocorticotropic hormone (ACTH) in mice. We have demonstrated that the administration of rhIL-6 alone does not duplicate the stimulatory effect of rhIL-1 alpha on ACTH release. On the other hand, suboptimal amounts of rhIL-1 alpha and rhIL-6 synergize to induce an early (30-60 min) ACTH response and produce a later (2-3 h) response that is similar to the one observed after rhIL-1 alpha is administered alone. These results suggest that the 2-3 h response to rhIL-1 alpha may be dependent on synergy with the endogenous IL-6 it induces systemically and in the central nervous system (including the hypothalamus and the pituitary gland).

Adrenocorticotropic Hormone↗
PubMed1990

Neuroendocrine responses to emotional stress: possible interactions between circulating factors and anterior pituitary hormone release.

We have shown that a psychological stressor can elicit increases in plasma AVP levels in normal human subjects. Since AVP can enhance the release of ACTH, and the pituitary gland is outside the blood-brain barrier, AVP present in the general circulation might extend the time course of stress-induced, CRF-mediated release of ACTH from the anterior lobe. Since PRA is involved in the synthesis of angiotensin I, the precursor of AII, and AII is known to enhance CRF-mediated release of ACTH from pituitary cells and to stimulate release of AVP, it is possible that the increase in PRA also contributed to the release of AVP and ACTH in this study. Reports differ as to whether circulating catecholamines can release ACTH in vivo by direct action on the pituitary. Finally, it has been reported that beta-EP enhances the release of PRL, and inhibits release of AVP. Since the increase in beta-EP in the present study was quite robust, it might have extended the PRL release, and truncated the AVP response.

Adrenocorticotropic Hormone↗
PubMed1990

The influence of fitness on neuroendocrine responses to exhaustive treadmill exercise.

Neuroendocrine and sympathoadrenal responses to exhaustive graded treadmill exercise were examined in 17 male subjects of varying degrees of fitness. The mean duration of exercise to exhaustion was 15.2 +/- 0.7 (+/- SE) min. Exercise duration was inversely correlated with baseline heart rate (P less than 0.05). Compared to standing baseline values, mean plasma norepinephrine and epinephrine levels increased 339% and 301%, respectively, in an integrated 2-min blood sample collected immediately after completion of exercise. Mean adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-EP), beta-lipotropin (beta-LPH), and prolactin levels increased 282%, 720%, 372%, and 211%, respectively, in an integrated 4-min blood sample beginning 2 min after completion of exercise. Cortisol levels increased 183% in the sample collected 17-21 min after exercise. The magnitude of these neuroendocrine responses to exercise was similar among individuals at the same relative intensity of exhaustive exercise, regardless of the duration of exercise. The exercise-induced increases of the pro-opiomelanocortin (POMC)-derived peptides, ACTH, beta-EP, and beta-LPH, were highly correlated with each other (P values less than 0.001), and were correlated with prolactin increases, (P values less than 0.05). During a 20-min recovery period after exercise, changes in heart rate, ACTH, and beta-LPH levels were correlated with duration of exercise, (P less than 0.01, P less than 0.03, and P less than 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1990

Effects of social conflict on POMC-derived peptides and glucocorticoids in male golden hamsters.

The effects of fighting and footshock on circulating adrenocorticotropin-like immunoreactivity (ACTH-LI), cortisol, corticosterone, beta-endorphin-like immunoreactivity (beta-EP-LI), and beta-lipotropin-like immunoreactivity (beta-LPH-LI) were examined. In the first experiment, catheterized males were paired with large, ovariectomized females for 15 min. Submissive males exhibited significant increases in plasma ACTH-LI, cortisol, corticosterone, and beta-EP-LI. In the second experiment, two males were paired to determine whether the hormonal response in submissive animals was different from that in dominant hamsters. The pattern and magnitude of the hormonal response was also compared to that following a commonly used stressor-footshock. Footshock was associated with large increases in each of the plasma hormones measured. Submission, but not dominance, was associated with smaller, but still significant, increases in ACTH-LI, cortisol, beta-EP-LI and beta-LPH-LI. The data indicate that fighting is not a generalized stressor. "Losing," in particular, appears to be an example of a biologically relevant stressor.

Adrenocorticotropic Hormone↗
PubMed1990

Hyperresponsiveness of the rat neuroendocrine system due to repeated exposure to stress.

Sequential exposure to stressors may elicit a period of endocrine hyperresponsiveness during which plasma hormone concentrations reach higher levels after repeated exposure to a stressor compared to levels after initial exposure. The present study was designed to further characterize hyperresponsiveness to repeated stress and determine if hyperresponsiveness is dependent upon repeated exposure to the same stressful stimuli. In Experiment 1, rats were stressed by inescapable tailshock, immobilization or exposure to shock chamber without shock for one, two, three, four or five consecutive days (15 min/day). In rats exposed to tailshock, corticosterone (CS) levels in plasma collected on days 2, 3, 4 and 5 were higher than CS levels following acute tailshock on day 1, demonstrating hyperresponsiveness to repeated tailshock. Hyperresponsiveness of CS secretion also occurred in groups of rats restrained for four or five days. No changes occurred in the CS response of animals repeatedly exposed to immobilization. Prolactin (PRL) levels were not affected by repeated exposure to the stressors. However, PRL values were different between the stress conditions and indicated that the order of stressor severity was tailshock greater than immobilization greater than exposure to shock chamber without shock. In Experiment 2, rats were exposed to either one or two consecutive days of tailshock or immobilization. Other rats were exposed to either tailshock or immobilization on the first day, then switched to the other stressor on the next day. Hyperresponsiveness to repeated tailshock, but not immobilization, was reflected in plasma levels of CS and adrenocorticotropic hormone (ACTH), but not PRL. Hyperresponsiveness of CS and ACTH secretion also was found in rats first stressed by immobilization then switched to tailshock, demonstrating that hyperresponsiveness is not dependent upon reexposure to familiar stressful stimuli. However, hyperresponsiveness did not occur in rats first exposed to tailshock then switched to immobilization. The data suggest that both immobilization and tailshock primed the organism to hyperrespond, but only the more severe stressor (tailshock) elicited hyperresponsiveness of the neuroendocrine system.

Adrenocorticotropic Hormone↗
PubMed1989

Dexamethasone suppresses ACTH release without attenuating pituitary cyclic AMP response to stress in vivo.

Dexamethasone, a synthetic glucocorticoid, has been shown to decrease basal and stress-elevated levels of the pituitary hormone ACTH. Glucocorticoids are known to bind to multiple sites within the brain and pituitary and it is not known which site(s) is most important in mediating the observed inhibition of ACTH release. At the level of the corticotroph, there is contradictory data from in vitro studies regarding whether dexamethasone acts proximal or distal to the formation of the cyclic AMP second messenger that has been shown to be involved in CRF-stimulated ACTH release. In the present report, we have examined the effects of dexamethasone pretreatment on stress-induced elevations in pituitary cyclic AMP and the release of ACTH in vivo. Acute stress (15 min of intermittent footshock) elevated levels of pituitary cyclic AMP and plasma ACTH consistent with previous studies. Dexamethasone administration (0.4 mg/kg 24 hr prior to sacrifice plus 0.2 mg/kg 2 hr prior to sacrifice) inhibited stress-induced elevations in plasma ACTH but did not affect pituitary cyclic AMP response to acute stress. These findings suggest that dexamethasone inhibits the release of ACTH via an action distal to the generation of cyclic AMP.

Adrenocorticotropic Hormone↗
PubMed1989

ACTH, prolactin, corticosterone and pituitary cyclic AMP responses to repeated stress.

The present experiment was conducted to determine whether the plasma hormonal and pituitary cyclic AMP responses observed following a single exposure to an acute stressor would diminish following reexposures to the same stressor. Fifteen-min stress exposures (forced running) were separated by 45-min recovery periods. Separate groups of control and stressed animals were sacrificed before and after each of four 15-min stress periods and after each recovery period. The first exposure to 15 min of forced running raised plasma ACTH, corticosterone and pituitary cyclic AMP levels approximately 6-fold and more than tripled levels of plasma prolactin. Plasma ACTH and pituitary cyclic AMP responses to the second, third and fourth stress exposures were very similar to the responses to the first stress exposure, and levels of these substances returned to prestress levels during each 45-min recovery period. Plasma prolactin responses to the four stress sessions were somewhat variable but no significant trend among the responses was seen. Plasma prolactin levels also returned to prestress levels between stress exposures. Corticosterone levels were similar following each of the four stress sessions but levels remained elevated compared to prestress levels between stress exposures. These data suggest that pituitary responses to acute stress are rapid, that return to prestress levels is also rapid, with the exception of corticosterone, and that repeated responses of the same magnitude may be evoked when stressors are separated by short recovery periods.

Adrenocorticotropic Hormone↗