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Journal Article 2012; 33(2): 124-132 PubMed PMID: 22592192 Citation  Keywords:  Animals, Gene Expression:physiology, Hypothalamo-Hypophyseal System:physiology, Male, Myocardium:cytology, Pituitary-Adrenal System:physiology, Protein Transport, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Rats, Wistar, Receptors, Oxytocin:biosynthesis.   

OBJECTIVES: Cardiovascular system is regulated by a diverse array of hormones, neurotransmitters and neuropeptides. Oxytocin and its receptors (OTR) were also shown to regulate cardiovascular functions and this hormone was even called cardiovascular hormone. In recent publication, we demonstrated the expression of mRNA of OTR by real-time quantitative PCR (RT qPCR) in all rat heart compartments. The aim of this study was to investigate the effects of acute restraint stress on OTR mRNA expression in two rat strains with different activity of HPA axis.

METHODS: Adult male Sprague-Dawley and Lewis rats, the latter strain reported to have lower HPA activity, were used in RT qPCR studies and Wistar rats in immunofluorescent ones. Both acute restraint (IS) and this stress combined with the immersion of rats in water (ICS) lasted 60 min. Gene expression of OTR mRNA was estimated in all heart compartments after 1 or 3 hours after stress termination (IS1, IS3, ICS1, ICS3). The relative expression was calculated using 2(-ΔΔC)T method. In immunofluorescent studies we used commercial specific OTR antibodies.

RESULTS: In RT qPCR studies we found higher expression of OTR mRNA in atria than in ventricles and no statistical differences between Sprague-Dawley and Lewis rats under basal conditions. Relative expression of OTR mRNA after 60 min lasting stress exposure differed in dependence on the stress type and partly on the time interval after the stress termination. When compared to controls, in rat left atria both stressors caused inhibition of OTR mRNA expression in both rat strains. In rat ventricles, which have very low OTR mRNA expression, there was a significant difference in the effect of two stressors. In most groups ICS displayed the increase of OTR mRNA expression if compared to IS groups. Immunofluorescent studies revealed changes induced by acute restraint stress in all heart compartments. The immunofluorescent studies suggested that acute stress induces higher colocalization of OTR with the nuclei than it was observed in the controls.

CONCLUSIONS: The expression of OTR mRNA in all heart compartments of controls as well as after stress exposure in Sprague-Dawley and Lewis rats support the notion that OTR plays a regulatory role in the cardiovascular system and is also involved in the regulations in the heart after stress. The immunofluorescent observation that OTRs coexpress in areas of cell nuclei in certain heart compartments and after acute stress, compared to controls, requires further studies....

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Journal Article 2011; 32(6): 805-810 PubMed PMID: 22286791 Citation  Keywords:  Animals, Hypothalamo-Hypophyseal System:physiology, Male, Myocardium:cytology, Oxytocin:metabolism, Pituitary-Adrenal System:physiology, RNA, Messenger:metabolism, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Receptors, Oxytocin:genetics,.   

OBJECTIVES: Oxytocin (OT) is a neuropeptide acting both as a peripheral hormone and in the brain as neurotransmitter and neuromodulator. In addition to its well-known effects on milk-ejection and uterine contraction, OT was shown to exert neuroendocrine regulation of heart functions. The aim of this study was to investigate the expression of mRNA of OT receptors (OTR) in rat hearts by real-time quantitative PCR (qPCR). The study was performed in Sprague-Dawley (SD) and Lewis (LE) rat strains, the latter having lower activity of HPA axis.

METHODS: We used adult male SD and LE rats. OTR mRNA expression was detected in all heart chambers by comparing their threshold cycle values (CT) to CT of reference gene β-actin. The relative expression ratios were calculated using the 2-ΔΔCT method. The specificity of reaction of primary antibody with OTRs was tested by Western Blot and localization of OTR in the heart compartments was performed by immunofluorescence with commercial OTR specific antibodies.

RESULTS: We found expression of OTR mRNA in all heart compartments. The expression of OTR mRNA in both atria (LA, RA) was much higher than in the ventricles (RV, LV). By using two-way ANOVA we found no statistical differences between corresponding compartments of SD and LE rats. Immunohistochemical studies showed that OTR staining is not related to neuronal tissue and findings from left atrium indicate that prevalent localization of OTR is on cell membranes of cardiomyocytes.

CONCLUSIONS: The finding of expression of OTR mRNA by real-time qPCR and proof of OTR staining by immunohistochemistry in all heart compartments indicate that OT and its receptors may have function as a cardiovascular hormone. The differences in the HPA axis activity, as is exemplified in Sprague-Dawley and Lewis rat strain, do not project in the expression of OTR mRNA under basal condition. The effect of activity of HPA on OTR expression should be studied under stimulated conditions as it was performed in the behavioral studies....

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Journal Article 2011; 32(4): 475-480 PubMed PMID: 21876512 Citation  Keywords:  Adult, Biomarkers:metabolism, Circadian Rhythm:physiology, Dehydroepiandrosterone Sulfate:metabolism, Humans, Hydrocortisone:metabolism, Hypothalamo-Hypophyseal System:physiology, Male, Pituitary-Adrenal System:physiology, Reference Values, Saliva:metabol.   

OBJECTIVES: Because the cortisol awakening response (CAR) has received increasing attention as a useful index of adrenocortical activity, the primary objective of this study was to investigate the presence of an awakening response for various salivary biomarkers of adrenocortical activity, including dehydroepiandrosterone-sulphate (DHEA-S), which acts as a cortisol antagonist, and α-amylase, which is a predictor of circulating catecholamine activity. Salivary biological indicators are considered to be valuable markers of hypothalamus-pituitary-adrenal (HPA) axis diurnal activity.

METHODS: In an attempt to overcome problems associated with non-adherence to the requested sampling protocol, only young, healthy males with a physiological CAR value (defined as a 50% increase in salivary cortisol within 30 min after waking) were included in the study (67 out of 102 who initially enrolled met this criterion).

RESULTS: Our results suggested that, as is already known for cortisol, DHEA-S and α-amylase have significant awakening responses. In addition, daily profile of salivary cortisol, α-amylase and DHEA-S fluctuations were analysed. Significant correlations were found between salivary cortisol, DHEA-S and α-amylase levels. The results showed that cortisol and DHEA-S concentrations were inversely correlated with α-amylase levels.

CONCLUSION: This correlation confirmed the distinctiveness of the two regulatory systems: salivary cortisol and DHEA-S concentrations reflect the activity of the HPA axis, whereas α-amylase activity is more closely related to sympathetic activity. In addition, the present study emphasizes the potential value of saliva collection (which is both easy and stress-free) in monitoring changes of adrenal function, confirming that multiple sampling (especially within 1 h after awakening) is necessary to reliably characterise biomarker activity when investigating neuroendocrine changes under various conditions....

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Journal Article 2011; 32(1): 64-76 PubMed PMID: 21407163 Citation  Keywords:  Adrenalectomy, Animals, Avoidance Learning:drug effects, Corticosterone:blood, Corticotropin-Releasing Hormone:blood, Hypothalamo-Hypophyseal System:physiology, Male, Maze Learning:drug effects, Memory, Short-Term:drug effects, Pituitary-Adrenal System:ph.   

OBJECTIVES: Stress activates the hypothalamic-pituitary-adrenal (HPA) axis. This activation is executed mainly through the release of corticosteroids from adrenal that subsequently exert negative feedback on corticosterone-releasing hormone (CRH) production. The effects of corticosterone on learning and memory has been studied intensively. Less is known about the effect of CRH on cognitive phenomena.

DESIGN AND SETTING: The present study aimed at studying the separate effects of stress cascade hormones, namely CRH and corticosterone, on learning and memory in a battery of learning tasks.

RESULTS: Long-term administration of CRH led to a transient impairment of spatial performance in the active allothetic place avoidance (AAPA) task requiring cognitive coordination, whilst co-application of CRH and corticosterone resulted in permanent impairment in this task. Corticosterone alone impaired the long-term retention of passive avoidance. CRH alone exerted no effect on the working memory version of the Morris water maze (MWM) and inhibitory avoidance.

CONCLUSIONS: Our results suggest differential effects of stress cascade hormones on various types of behavior....

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Journal Article 2008; 29(1): 159-162 PubMed PMID: 18283263 Citation  Keywords:  Adrenocorticotropic Hormone:blood, Animals, Body Weight:physiology, Central Nervous System:physiology, Circadian Rhythm:physiology, Corticosterone:blood, Entorhinal Cortex:physiology, Hypothalamo-Hypophyseal System:physiology, Male, Pituitary-Adrenal Syst.   

OBJECTIVE: In our previous study, a lesion in the entorhinal cortex was found to significantly attenuate the elevation of adrenocorticotropic hormone (ACTH) in plasma during immobilization stress. The aim of the present study was to investigate whether the entorhinal cortex exerts a modulatory effect on circadian ACTH and corticosterone release.

MATERIALS AND METHODS: Ibotenic acid (15 microg/microl) was stereotaxically bilaterally injected into the entorhinal cortex of rats. Two weeks after the injections, ACTH and corticosterone levels in plasma were measured at 0800 h, 1300 h and 1800 h.

RESULTS: Compared with sham-operated control rats, rats with entorhinal cortex lesions produced by ibotenic acid showed either significantly elevated plasma ACTH or plasma corticosterone levels at 0800 h, but no difference at 1300 h or 1800 h.

CONCLUSION: The results of the present study indicate that the entorhinal cortex plays a certain role in the regulation by the central nervous system of the circadian rhythm of the hypothalamic-pituitary-adrenal (HPA) axis....

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Journal Article 2007; 28(5): 585-590 PubMed PMID: 17984949 Citation  Keywords:  Adaptation, Psychological:physiology, Aggression:physiology, Animals, Corticosterone:blood, Dominance-Subordination, Hypothalamo-Hypophyseal System:physiology, Male, Mice, Mice, Inbred BALB C, Social Environment, Stress, Psychological:blood, Territorialit.   

OBJECTIVE: Social stressors modulate the hypothalamic-pituitary-adrenal axis in rodents. However, reports on the association between corticosterone level and behavioural responses to the stressor are ambivalent. This may depend on the experimental paradigm, species- and strain-differences, duration of exposure to the stressor, but also on using either the social state (dominant or subordinate) or the coping style (proactive or passive) of an animal to correlate the corticosterone level with.

DESIGN AND SETTING: We used male Balb-C mice in a resident-intruder paradigm. Adolescent intruders (aged five to eight weeks) were transferred into the cage of an adult resident (aged about four month) for five minutes. The interactions were video-taped for behavioural analysis. Ten minutes after the encounters, intruders were sacrificed and blood samples were collected.

RESULTS: Dominant intruders showed offensive behaviours (attack, chase, tail tracking) and won most of the fights, whereas subordinate intrudes showed mainly submissive behaviours (flight, freezing) and were further classified into active and passive subordinates. Active subordinates displayed significantly more flight-behaviour than passive subordinates. Dominant intruders showed significantly higher post-stress levels of corticosterone than subordinates, which did not differ from control mice, which experienced five minutes of novel-cage exposure. Comparing all three behavioural phenotypes we found the lowest corticosterone levels in active subordinates.

CONCLUSION: Social state significantly affects the HPA-axis response to acute social stressors....

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Clinical Trial 2006; 27(4): 433-437 PubMed PMID: 16892008 Citation  Keywords:  Adult, Anxiety:physiopathology, Depression:physiopathology, Dexamethasone, Feedback, Physiological:drug effects, Follow-Up Studies, Glucocorticoids, Humans, Hydrocortisone:blood, Hypothalamo-Hypophyseal System:physiology, Immunosuppression, Male, Pituitar.   

OBJECTIVES: Higher rates of dexamethasone test (DST) nonsuppression in schizophrenia have been attributed to depressive symptoms, suicidality and negative symptoms. No study concerning first-episode schizophrenia has yet been published.

DESIGN: In patients hospitalised for the first time with first-episode schizophrenia the DST has been performed before, at the end of the acute treatment and after one year. At the same time the clinical evaluation with PANSS was performed. A cortisol value >5 microgram/dl in either of the postdexamethasone samples indicated nonsuppression of cortisol.

RESULTS: A total of 56 males were included. 18% of pts were DST nonsuppressors at medication-free baseline, 5% and 16% after acute treatment and after one year respectively. After 1 year 42/56 of patients fulfilled the criteria of remission. The rate of nonsuppression was 21.4%, 5% and 16.4% in remitters and 7%, 7% and 14.3% in nonremitters. Significant differences in the whole group were found between postdexamethasone cortisolemia at discharge on the one hand and on admission and at the one-year follow-up on the other. Significant correlations were observed between postdexamethasone cortisolemia and negative symptoms at the end of acute treatment.

MAIN FINDINGS: In first-episode schizophrenia the short-term treatment led to a decrease in cortisolemia and rates of nonsuppression and an increase at a one-year follow-up.

CONCLUSIONS: Rates of DST nonsuppression in schizophrenia including first-episode schizophrenia are influenced by the stage of illness and medication status. The impairment of feedback regulation of cortisol secretion may be related to different biopathogenetic mechanisms depending on the phase of the illness....

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Journal Article 2005; 26(4): 342-346 PubMed PMID: 16136012 Citation  Keywords:  Abortion, Spontaneous:blood, Adrenocorticotropic Hormone:blood, Cystinyl Aminopeptidase:blood, Female, Homeostasis:physiology, Humans, Hypothalamo-Hypophyseal System:physiology, Pituitary-Adrenal System:physiology, Pregnancy, Pregnancy Trimester, First,.   

INTRODUCTION: The labor at term finishes normal pregnancy. Both labor at term and first trimester spontaneous abortion are connected with increasing cytotoxic immune response within decidua. Th1 cytokines including IL-2 and INF-gamma are able to exert an effect on HPA axis and result in ACTH secretion. Oxytocinase serum level during pregnancy rises with the fetal development and arrest of oxytocinase serum growth might indicate the its development impairment, what might result in spontaneous abortion.

MATERIAL AND METHODS: The study group consisted of 27 patients with clinical symptoms of missed abortion. A control group consisted of 89 pregnant women, who were successfully treated because of infertility. Immunoassay was used to measure ACTH plasma concentration. Oxytocinase plasma activity was established using l-cystine-di-beta-naphthylamide as a substrate.

RESULTS: In the present study, significant increase in ACTH plasma concentration was observed during first trimester of spontaneous abortion. These patients were not characterized by significant increase of oxytocinase plasma level.

CONCLUSIONS: The observed ACTH rise during spontaneous abortion might be also related to the alterations at the maternal-fetal interface and the response of HPA axis to the growing cytotoxic activity....

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