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Biomedical subjects

E A Young

Publications and source records attributed to E A Young.

At least 19 recordsLinked to original sources
PubMed2003

Hypothalamic-pituitary adrenal response to cholecystokinin-B receptor agonism is resistant to cortisol feedback inhibition.

Intravenous injection of the cholecystokinin (CCK)-B receptor agonist, pentagastrin, produces robust, dose-dependent release of adrenocorticotropin (ACTH) and cortisol, supporting the hypothesis that CCK-B agonists pharmacologically activate the hypothalamic-pituitary-adrenal (HPA) axis. The mechanism of activation and its physiological relevance remain uncertain. Preliminary data suggest that the ACTH response to pentagastrin may be differentiated from the response to exogenous corticotropin releasing hormone (CRH) by its relative resistance to cortisol feedback inhibition. To more directly test the relationship between cortisol levels and ACTH response to pentagastrin, this study examined responses to pentagastrin (a) during a peak (8 a.m.) and a nadir (4 p.m.) period of endogenous cortisol secretion and (b) when cortisol levels were artificially reduced to low levels by administration of metyrapone. ACTH responses to pentagastrin were identical in the morning and afternoon, despite substantial differences in basal cortisol levels. Suppression of cortisol with metyrapone had little impact on ACTH response to pentagastrin. These data support the hypothesis that CCK-B receptor mediated activation of the HPA axis is relatively resistant to cortisol feedback inhibition. This differentiates it from CRH-mediated activation and raises the possibility that CCK could contribute to acute activation of the HPA axis even in the face of elevated basal cortisol levels, such as those seen in chronic stress or some psychiatric disorders.

Adrenal Glands↗
PubMed2003

Local recurrence of breast cancer following surgery and radiotherapy: incidence and outcome.

Local recurrence of cancer in the treated breast following breast-conserving surgery and radiotherapy occurs in a minority of patients, but can represent a significant clinical problem. The impact of local relapse on the subsequent course of the disease is disputed. The aim of this retrospective review was to identify the rate and prognostic factors for breast recurrence and to determine the subsequent outcome. The case notes of 2159 patients treated between 1989 and 1992 were reviewed. Actuarial local relapse rate was 6.3% at 5 years. Factors predictive for recurrence on multivariate analysis were age (P<0.001), status of excision margins (P=0.019), and pathological UICC stage (P=0.01). One hundred and sixty-one patients developed local recurrence in the treated breast of whom 101 were treated with further surgery. The 5-year cancer-specific survival of this group was comparable with that of the patients who remained free of breast relapse (82 vs. 88%) but subsequently fell to 61 vs. 80% at 8 years (P<0.001). Sixty patients were unable to have salvage surgery; their cancer-specific survival was much worse than that of patients with operable recurrences at 33% at 5 years and 13% at 8 years. Eighty-three patients (4% of the original 2159 patients) had uncontrolled local disease at time of death or last follow-up. The prognosis of patients who developed recurrence within 2 years of their initial treatment was inferior to those who developed recurrences after 4 years (cancer-specific survival 5 years post-recurrence 23 vs. 57% P=0.008). Systemic therapy should be considered for patients with early breast recurrence in view of their inferior survival.

Adult↗
PubMed2002

Basal circadian cortisol secretion in women with temporomandibular disorders.

Muscular temporomandibular disorder (TMD) is a common stress-related condition showing marked comorbidity with depression and fibromyalgia (FM), both of which are associated with dysregulation of cortisol secretion. We measured cortisol levels in 15 women with well-defined TMD and 15 matched controls by sampling blood at 10-minute intervals over 24 hours in a controlled environment. TMD patients showed markedly increased daytime cortisol levels 30% to 50% higher than those of controls (p = 0.0032) and a one-hour phase delay in the timing of maximum cortisol levels (p = 0.048). Increased activation of the stress hormone axis by conscious pain perception is a likely explanation, but the magnitude of the increase could indicate that pain in the facial region acts as a greater stimulus than pain elsewhere in the body.

Adrenal Cortex↗
PubMed2001

Effect of ruminations on the saliva cortisol response to a social stressor.

Depression is generally precipitated by stressful life events, which suggests that there could be differences in response to stress in individuals at risk for depression compared to normal subjects. To test this hypothesis, we compared individuals who scored high on ruminative coping, a risk factor for depression, to individuals low on ruminative coping. We used the Trier Social Stress Test (TSST), a mock job interview in front of a panel of judges, and collected saliva cortisol to assess neuroendocrine response. While we observed a clear effect of the stressor on saliva cortisol secretion, we observed no differences in this response between high and low ruminators. However, the task itself failed to cause a significant increase in rumination in either group, suggesting the task itself may not be optimal for testing the hypothesis. Finally, a modified version of the TSST in which the subjects were allowed a longer preparatory period resulted in a markedly diminished saliva cortisol response to the TSST.

Adaptation, Psychological↗
PubMed2001

Twenty-four-hour ACTH and cortisol pulsatility in depressed women.

Increased plasma cortisol in patients with major depression is a well documented finding, although it is present in only 25-30% of subjects with major depression. However, ACTH and cortisol are secreted in a pulsatile manner, so it is unclear if increased ACTH secretion occurs in depression and if there are changes in the pulsatile components of ACTH secretion. Ten-minute sampling for ACTH and cortisol was performed for 24 hr in 25 premenopausal depressed women, whose age and menstrual cycle day matched control women. As a group, the depressed women demonstrated a trend to increase cortisol secretion (p = 0.089). There was no difference in mean cortisol between the patient group as a whole (8.36 +/- 2.9 microg/dl) and those patients meeting criteria for atypical depression (8.38 +/- 1.9 microg/dl), but patients meeting criteria for endogenous showed increased cortisol (12.17 +/- 4 microg/dl) Mean ACTH was not significantly different between patients and controls. Pulse analyses revealed similar number of secretory events and similar amplitudes for cortisol secretory bursts in patients and controls. The baseline component area under the curve of cortisol secretion was increased at a trend level (p =.064) in depressed patients, and the baseline AUC for ACTH was significantly increased in depressed patients (p =.045). No differences were found in pulsatile components of ACTH secretion between patients and matched controls. Harmonic analyses indicated no significant differences between patients and controls on any detected rhythm for ACTH or cortisol. These data suggest that the pulsatile and circadian components of the HPA axis are normal in premenopausal depressed women and that only 24% of depressed women demonstrate hypercortisolemia.

Adrenocorticotropic Hormone↗
PubMed2001

Effects of estrogen antagonists and agonists on the ACTH response to restraint stress in female rats.

Previous studies have found that female rats are less sensitive than males to hypothalamic-pituitary-adrenal axis feedback inhibition by exogenous glucocorticoid administration. To determine whether estrogen contributes to this sex difference, we examined the effects of the estrogen antagonists tamoxifen and C1628 on the ACTH and corticosterone responses to restraint stress. CI628 increased both the ACTH and corticosterone response to restraint stress, and tamoxifen increased the ACTH response to restraint. Using overiectomized female rats, we also examined the effects of seven days of estradiol and/or progesterone replacement. Low dose estradiol decreased the ACTH but not the corticosterone response to restraint stress while progesterone had no effect on ACTH or corticosterone responses. The combination of estradiol and progesterone also decreased the ACTH response to stress, and the magnitude of the effect did not differ from that found with estradiol treatment alone. These data suggest that in the physiological range estradiol is an important inhibitory factor in the hypothalamic-pituitary-adrenal stress response of females.

Adrenocorticotropic Hormone↗
PubMed2001

Family functioning, peer influence, and media influence as predictors of bulimic behavior.

One hundred and twenty undergraduate women students reported their height and weight and completed the Eating Disorder Questionnaire (EDQ), the Eysenck Personality Inventory (EPI), the Beck Depression Inventory (BDI), the Family Assessment Device (FAD), the Body Shape Questionnaire (BSQ), the Body Image Assessment (BIA), and measures of peer and media influence. Family functioning was shown to be a poor predictor of bulimic behavior, whereas peer influence was a significant predictor. Media influence interacted with body dysphoria to increase the likelihood of bulimic behavior. The BSQ was a better predictor of bulimic behavior than the BIA, suggesting that students' responses to a measure that asks questions about specific areas of the body may reflect their feelings of body dysphoria more accurately than a measure that relies on a generalized silhouette.

Journal Article↗
PubMed2000

Similarity in saliva cortisol measures in monozygotic twins and the influence of past major depression.

BACKGROUND: Some studies suggest that cortisol may be under genetic control. The aims of our study were to investigate the familial resemblance in morning and evening cortisol secretion as assessed by saliva cortisol and to assess the influence of history of major depression. METHODS: Women for this investigation were selected from an ongoing study in female-female twin pairs ascertained from the Virginia Twin Registry. Telephone screening assured that current inclusion/exclusion criteria were met. Subjects were asked to collect AM samples within 45 min after awakening, and evening samples immediately before bedtime for 14 days. RESULTS: There was a high degree of correlation across weeks in both the AM and PM cortisol values, indicating significant stability across individuals. There was significant correlation between AM and PM cortisol in monozygotic twins. In twins with a history of major depression (n = 30), compared with the twins without past major depression (n = 28), there was a trend towards higher cortisol (p = .056). CONCLUSIONS: These results suggest that around 40-45% of the total variance in salivary cortisol is shared by monozygotic twins. Although the increase in baseline cortisol in twins with a history of major depression is only significant at the trend level, the effect size is comparable to an "in episode" depressed population.

Adult↗
PubMed2000

Alterations in hippocampal GAP-43 phosphorylation and protein level following contextual fear conditioning.

C57BL/6 (B6) mice display better contextual learning than the DBA/2 (D2) mice. The possibility that GAP-43, is differentially affected as a function of strain and learning was investigated in the present study. No basal difference between C57BL/6J (B6) and DBA/2J (D2) mice in the amount of hippocampal GAP-43 was observed, but naive D2 mice have slightly lower basal levels of GAP-43 phosphorylation than do B6 mice. Interestingly, alterations in hippocampal GAP-43 protein levels and phosphorylation state in response to training for contextual learning were observed only in B6 mice. Immediate-shocked mice, serving as nonlearning controls, showed no GAP-43 alterations, nor did D2 mice subjected to either training condition. These results suggest that modulation of hippocampal GAP-43 may be important for contextual learning and that strain-specific alterations in GAP-43 may be part of a disrupted pathway in D2 mice that is essential for learning.

Acoustic Stimulation↗
PubMed2000

Alteration in the hypothalamic-pituitary-ovarian axis in depressed women.

BACKGROUND: Stress and corticotropin-releasing hormone inhibit the reproductive axis. We hypothesized that reproductive axis hormone secretion, particularly luteinizing hormone secretion, is inhibited in women with depression, similar to what has been observed to be caused by stress in numerous species. METHODS: Blood samples were collected every 10 minutes for 12 hours in 25 untreated premenopausal women with depression and 25 nondepressed women who were matched by age and menstrual cycle day. Samples were assayed for luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone. RESULTS: The mean plasma estradiol level was 30% lower in the follicular phase in women with depression than in their matched controls: 191 + 136 vs 261 + 169 pmol/L (52 + 37 vs 71 + 46 pg/mL). The half-life of luteinizing hormone was significantly shorter in women with depression than in their matched controls during both the follicular (22% shorter) and luteal (15% shorter) phases. CONCLUSIONS: The blood levels of reproductive hormones were mostly normal in women with depression, but the blood level of estradiol was significantly lower. Estradiol is known to affect a number of neurotransmitter systems in the brain. Arch Gen Psychiatry. 2000;57:1157-1162.

Adult↗
PubMed2000

Hormonal evidence for altered responsiveness to social stress in major depression.

In patients with major depression, abnormalities in baseline cortisol secretion and resistance to negative feedback are well established. However, it is unclear if patients with major depression have alterations in the hypothalamic-pituitary-adrenal (HPA) response to stressors. While other challenges to the HPA axis have used endocrine stimuli such as insulin-induced hypoglycemia, we now report of the response to a social stressor in patients with major depression and matched control subjects. We used the Trier Social Stress Test (TSST), a public speaking task followed by mental arithmetic challenge in front of a panel of judges. The results suggest that depressed patients manifest normal cortisol response to a social stressor, despite increased pre-stressor plasma cortisol. However, the beta-endorphin response to the TSST was significantly smaller in the depressed patients compared to matched controls. These data are similar to data found with exogenous corticotropin-releasing-hormone challenge studies and suggest that elevated baseline cortisol can modulate the pituitary corticotroph response to a stressor, but that changes in adrenal sensitivity to ACTH result in a robust cortisol response to this stressor.

Adult↗
PubMed2000

Follicular phase hypothalamic-pituitary-gonadal axis function in women with fibromyalgia and chronic fatigue syndrome.

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are clinically overlapping stress associated disorders. Neuroendocrine perturbations have been noted in both syndromes, and they are more common in women, suggesting abnormalities of gonadal steroid hormones. We tested the hypothesis that women with FM and CFS manifest abnormalities of the hypothalamic-pituitary-gonadal (HPG) hormonal axis. METHODS: We examined the secretory characteristics of estradiol, progesterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH), including a detailed analysis of LH in premenopausal women with FM (n = 9) or CFS (n = 8) during the follicular phase of the menstrual cycle compared to matched healthy controls. Blood was collected from an indwelling intravenous catheter every 10 min. over a 12 h period. LH was assayed from every sample; pulses of LH were identified by a pulse-detection program. FSH and progesterone were assayed from a pool of hourly samples for the 12 h period and estradiol from samples pooled over four 3 h time periods. RESULTS: There were no significant differences in FSH, progesterone, or estradiol levels in patients versus controls. There were no significant differences in pulsatile secretion of LH. CONCLUSION: There is no indication of abnormal gonadotropin secretion or gonadal steroid levels in this small, but systematic, study of HPG axis function in patients with FM and CFS.

Adolescent↗
PubMed1999

Serotonin 1A receptor messenger RNA regulation in the hippocampus after acute stress.

BACKGROUND: When rats are subjected to chronic stress for 2 weeks, a significant decrease in hippocampal serotonin (5-HT)1A messenger RNA (mRNA) is observed. We wanted to investigate whether stress, administered for shorter periods of time, would result in decreases in 5-HT1A gene expression in hippocampus. METHODS: In one experiment, rats were either stressed daily for 1 week or implanted with two corticosterone pellets to produce elevated corticosterone levels. In another experiment, rats were subjected to a severe acute stressor and sacrificed 1 day or 1 week after the stressor. RESULTS: We found that 24 hours after the acute stress, rats showed a significant decrease in 5-HT1A mRNA levels in CA1 and the dentate gyrus compared to controls. No significant changes in 5-HT1A mRNA levels were detected in any of the other groups. CONCLUSIONS: Although 1 week of chronic stress is not sufficient to cause significant decreases in hippocampal 5-HT1A mRNA levels, a severe and prolonged acute stress is capable of down-regulating, at least transiently, 5-HT1A mRNA gene expression in hippocampus.

Acute Disease↗
PubMed1999

Neuroendocrine and psychophysiologic responses in PTSD: a symptom provocation study.

Biological research on post-traumatic stress disorder (PTSD) has focused on autonomic, sympatho-adrenal, and hypothalamo-pituitary-adrenal (HPA) axis systems. Interactions among these response modalities have not been well studied and may be illuminating. We examined subjective, autonomic, adrenergic, and HPA axis responses in a trauma-cue paradigm and explored the hypothesis that the ability of linked stress-response systems to mount integrated responses to environmental threat would produce strong correlations across systems. Seventeen veterans with PTSD, 11 veteran controls without PTSD, and 14 nonveteran controls were exposed to white noise and combat sounds on separate days. Subjective distress, heart rate, skin conductance, plasma catecholamines, ACTH, and cortisol, at baseline and in response to the auditory stimuli, were analyzed for group differences and for patterns of interrelationships. PTSD patients exhibited higher skin conductance, heart rate, plasma cortisol, and catecholamines at baseline, and exaggerated responses to combat sounds in skin conductance, heart rate, plasma epinephrine, and norepinephrine, but not ACTH. The control groups did not differ on any measure. In canonical correlation analyses, no significant correlations were found between response systems. Thus, PTSD patients showed heightened responsivity to trauma-related cues in some, but not all, response modalities. The data did not support the integrated, multisystem stress response in PTSD that had been hypothesized. Individual response differences or differing pathophysiological processes may determine which neurobiological system is affected in any given patient.

Acoustic Stimulation↗
PubMed1999

Differential regulation of hippocampal glucocorticoid receptors mRNA and fast feedback: relevance to post-traumatic stress disorder.

Hippocampal glucocorticoid receptors (GR and MR) play an important role in glucocorticoid negative feedback. Abnormalities in negative feedback are found in depression and in post-traumatic stress disorder (PTSD), suggesting that GR and MR might be involved in the pathophysiology of these disorders. Enhanced negative feedback, the PTSD-specific neuroendocrine abnormality, can be induced in animals using a single prolonged stress (SPS) paradigm (a number of different stressors in one prolonged session, 'no stress' interval and a testing session one week later). In the current study, we examined hippocampal GR and MR mRNA distribution in the same animals that exhibited altered negative feedback following the SPS. Seven groups of adult Sprague-Dawley male rats (seven animals each) were used in two studies, comparing unstressed controls to acutely stressed animals (SPS: 24 h group), SPS animals (seven and 14 days), and SPS + chronic stress animals. GR and MR mRNA distribution across hippocampal subfields was studied using in-situ hybridization with 35S-labelled cRNA probes. Acute stress produced down-regulation of GR and MR mRNA across all hippocampal subfields. Seven days later (SPS-7 group), there was a differential recovery, with GR mRNA reaching higher than the prestress levels, and MR mRNA remaining down-regulated. The same differential regulation was present in the 14-day group. Chronically stressed animals that exhibited normal fast feedback also had normalization in their GR and MR mRNA levels. The MR/GR ratio was decreased only in animals that had enhanced fast feedback. These findings suggest that the increase in GR, in hippocampus is involved in the fast feedback hypersensitivity observed in the SPS animals, and might also underlie enhanced dexamethasone sensitivity found in PTSD. Since differential activation of GR and MR can modulate memory, behavioural responsivity, anxiety and fear, change in MR/GR ratio might also explain other PTSD-related phenomena.

Animals↗
PubMed1998

Parallel modulation of striatal dopamine synthetic enzymes by second messenger pathways.

The activity of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in the striatum and their mRNA content in the midbrain were assayed in mice following the intracerebroventricular injection of forskolin or phorbol-12,13-myristic acid (PMA). Control and 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned animals were studied. Both forskolin and PMA induced a rapid and transient increase of tyrosine hydroxylase and aromatic L-amino acid decarboxylase activity in the striatum that lasted less than 45 and 60 min, respectively. A second belated increase of striatal tyrosine hydroxylase and aromatic L-amino acid decarboxylase activities was seen only after forskolin, and it was accompanied by a rise of tyrosine hydroxylase and aromatic L-amino acid decarboxylase mRNA in the midbrain. In the MPTP-lesioned mouse, the rise of tyrosine hydroxylase and aromatic L-amino acid decarboxylase following forskolin appeared exaggerated, while the response to PMA was not. These studies suggest that tyrosine hydroxylase and aromatic L-amino acid decarboxylase of striatum can be modulated in parallel by protein kinase A and protein kinase C, and that exaggerated responsiveness to protein kinase A is observed in the partially denervated striatum.

Animals↗
PubMed1998

The role of endogenous opioids in the luteinizing hormone surge in rats: studies with clocinnamox, a long-lasting opioid receptor antagonist.

Endogenous opioid peptides have been demonstrated to regulate luteinizing hormone (LH) secretion in a variety of species. Studies in rodents suggest a role of opioid peptide systems in controlling the timing of the LH surge, which is entrained to the circadian rhythm. The current studies utilize clocinnamox, a novel long-lasting opioid receptor antagonist that is capable of occupying mu-opioid receptors for periods of one week or more, to examine the role of endogenous opioid systems on the LH surge. Administration of clocinnamox [14b-(p-chlorocinamoylamino)-7,8-dihydro-N-cyclopropylmethyl normophineone mesylate]) on the morning of proestrus advanced the LH surge by several hours. Despite the blockade of opioid receptors and analgesia for more than one week, administration of clocinnamox on the evening of diestrus II had no effect on the timing of the LH surge but significantly increased plasma LH levels throughout the day of proestrus. These data suggest that removal of opioid tone is unlikely to be the critical signal controlling the initiation of the LH surge in rodents, although it does appear to be permissive for the surge. Furthermore, the mu-opioid receptor appears to be the receptor involved in the regulation of the LH surge.

Animals↗