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At least 883 records · Page 49Linked to original sources
PubMed2003

P but not R-axis interface is involved in cooperative binding of NAD on tetrameric phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus.

Homotetrameric phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Bacillus stearothermophilus can be described as a dimer of dimers with three non-equivalent P, R, and Q interfaces. In our previous study, negative cooperativity in NAD binding to wild-type GAPDH was interpreted according to the induced-fit model in terms of two independent dimers with two interacting binding sites in each dimer. Two dimeric mutant GAPDHs, i.e. Y46G/S48G and D186G/E276G, were shown to exhibit positive cooperativity in NAD binding. Based on the molecular modeling of the substitutions and the fact that the most extensive inter-subunit interactions are formed across the P-axis interface of the tetramer, it was postulated that both dimeric mutant GAPDHs were of O-P type. Therefore, the P-axis interface was assumed to play a major role in causing cooperativity in NAD binding.Here, two other mutant GAPDHs, Y46G/R52G and D282G, have been studied. Using small angle X-ray scattering, the dimeric form of the D282G mutant GAPDH is shown to be of O-R type whereas both dimeric mutant GAPDHs Y46G/R52G and Y46G/S48G are of O-P type. Similarly to dimeric Y46G/S48G mutant GAPDH, the dimeric Y46G/R52G mutant GAPDH exhibits positive cooperativity in NAD binding. On the other hand, no significant cooperativity in NAD binding to the dimeric form of the D282G mutant GAPDH is observed, whereas its tetrameric counterpart exhibits negative cooperativity, similarly to the wild-type enzyme. Altogether, the results support the view that the P-axis interface is essential in causing cooperativity in NAD binding by transmitting the structural information induced upon cofactor binding from one subunit to the other one within O-P/Q-R dimers in contrast to the R-axis interface, which does not transmit structural information within O-R/Q-P dimers. The absence of activity of O-P and O-R dimer GAPDHs is the consequence of a pertubation of the conformation of the active site, at least of the nicotinamide subsite, as evidenced by the absence of an ion pair between catalytic residues C149 and H176 and the greater accessibility of C149 to a thiol kinetic probe.

2,2'-Dipyridyl↗
PubMed1997

Active hypothalamic-pituitary-gonadal axis in an infant with X-linked adrenal hypoplasia congenita.

To evaluate the hypothalamic-pituitary-gonadal axis in an infant with adrenal hypoplasia congenita, we measured the serum levels of testosterone and performed a luteinizing hormone-releasing hormone stimulation test. The diagnosis was made because of the presence of a mutation, A300V, in the DAX-1 gene. The results demonstrated an active hypothalamic-pituitary-gonadal axis, with adult-level testosterone of 266 ng/dl on day 0, and maintenance of testosterone concentration in the 100 to 250 ng/dl range for 140 days as expected. The luteinizing hormone-releasing hormone lest was compatible with an active pituitary gland with a luteinizing hormone peak of 13.1 IU/L and a follicle-stimulating hormone of 5.0 IU/L We conclude that the DAX-1 mutation does allow a normal reproductive axis at birth. We speculate that sometime between infancy and puberty this mutation in the DAX-1 gene leads to an inability to activate the reproductive axis from its childhood suppression; thus puberty will not develop in this infant.

Adrenal Insufficiency↗
PubMed1986

The abnormal renal axis in children with spina bifida and gibbus deformity--the pseudohorseshoe kidney.

The axes of the kidneys in children with a thoracolumbar gibbus deformity may be distorted to simulate a horseshoe kidney. Measurements of the angle of the gibbus and the angle of intersection of the renal axes were made in 68 children with thoracolumbar meningomyelocele. Thirty-eight children with a gibbus deformity and thoracolumbar meningomyelocele had an abnormality of the renal axis on supine urography, including 19 (28 per cent) in whom a horseshoe kidney was suggested. Three additional children with a gibbus deformity and thoracolumbar meningomyelocele had a normal renal axis. Regression analysis of these data indicated a linear relationship between the angle of the gibbus and the amount of deviation of the renal axis for the values studied. Nuclear scintigraphy, ultrasound studies and clinical records were reviewed in all 41 children with a gibbus deformity. In none were the kidneys fused. There were 21 children with thoracolumbar myelomeningocele who had no gibbus deformity and a normal renal axis. Six other children will be described in detail, 2 of whom were excluded because of severe scoliosis and 4 with congenital renal anomalies.

Child↗
PubMed2000

Effects of acute alcohol intoxication on growth axis in human adolescents of both sexes.

We previously reported the deleterious effects of acute alcohol intoxication (AAI) on pituitary-gonadal and pituitary-adrenal axes hormones in human adolescents. In the present paper we studied the effects of AAI on the growth axis hormones, and the possible contribution of the insulin-glucose axis to the alcohol-induced dysfunction of the growth axis in human adolescents. Blood samples were drawn from adolescents that arrived at the emergency department with evident behavioural symptoms of drunkenness (AAI) or with nil consumption of alcohol (controls [C]). AAI produced in the adolescents of both sexes in our series: a decrease in growth hormone (GH) levels, without significant alteration of either insulin-like growth factor-I (IGF-I) or insulin-like growth factor binding protein-3 (IGFBP3); an increase in plasma glucose and a decrease in insulin in the female adolescents but not in the males. Males and females undergo a significant period of bone growth during adolescence. Growth axis hormones play an important role in the pubertal spurt. Thus, ethanol consumption during adolescence could have long-lasting deleterious effects on this aspect of development. In industrialised countries, around 35% of alcohol drinkers are under 16 years old, therefore the result of this study should be made known to adolescents and the appropriate authorities.

Adolescent↗
PubMed1998

Vasopressin and the regulation of hypothalamic-pituitary-adrenal axis function: implications for the pathophysiology of depression.

The role of arginine vasopressin (AVPNP) in the control of adrenocorticotropic hormone (ACTH) secretion is explored, and in particular, its involvement in various stress response paradigms which may be of relevance in our understanding of the pathophysiology of depression. VP is released from two sites in the hypothalamus; the parvicellular division of the paraventricular nucleus (PVN), where corticotropin releasing hormone (CRH) is also formed, and from the magnocellular neurons of the supraoptic nucleus (SON) and the PVN. The intricate interaction with CRH, the other main ACTH secretagogue, and with glucocorticoids, the inhibitory feedback component of hypothalamic-pituitary-adrenal-axis (HPA) activity, is outlined. That VP plays an important role in the stress response is now beyond doubt. Examination of the impact of psychological stressors on the differential expression of VP and CRH at a hypothalamic and pituitary level has been facilitated by advances in molecular biological techniques. Of importance has been the cloning of the V1b receptor gene, the receptor at which AVP is active in the anterior pituitary. Chronic stress paradigms, associated with HPA hyperresponsiveness, and ACTH release following a novel superimposed stress, have been found with relative consistency to show a shift in the CRH:AVP ratio. This may relate to differing feedback sensitivity of AVP to glucocorticoid feedback restraint and the greater responsivity of AVP over CRH to chronic stimulatory stress input. Evidence for functionally distinct pools of ACTH releasing corticotropes, and the finding that AVP levels more closely correlate with ACTH levels than do CRH levels, suggest a more dynamic role for AVP in activity of the stress axis, and a primarily permissive function for CRH. The renewed interest in the role of VP in HPA axis activity may have important implications for furthering our understanding of psychiatric conditions such as depression, where significant dysregulation of this axis is seen. Elevated baseline cortisol, dexamethasone non-suppression and blunted CRH/ACTH release have been consistently documented. The possible contribution of VP to this hyperactivity, despite its known synergy with CRH, has been largely neglected. In animal models there is clear evidence that chronic psychological stressors increase the ratio of AVP to CRH production. Psychosocial stressors are intrinsically linked with depressive illness. The finding of elevated levels of AVP in postmortem studies of depressives and the lowering of CSF AVP levels by antidepressants, raises the question of the precise role of AVP in the overactivity of the HPA in depression, a finding that is currently attributed to overdrive of its HPA regulatory companion, CRH.

Adrenocorticotropic Hormone↗
PubMed1996

Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in women with visceral and subcutaneous obesity: effects of the corticotropin-releasing factor/arginine-vasopressin test and of stress.

In a previous study, we demonstrated that premenopausal women with visceral obesity have hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by an exaggerated hormone response to corticotropin-releasing factor (CRF) and corticotropin (ACTH) stimulation. The hypothalamic peptide flow that stimulates the pituitary, particularly after a physiological stress challenge, involves not only CRF, but also arginine-vasopressin (AVP), which synergizes the CRF capacity to stimulate pituitary hormone secretion. Previous studies in humans have demonstrated that combining AVP with CRF permits maximal stimulation of the pituitary, providing a more appropriate method of assessing pituitary hormone reserve. We therefore investigated the response of the HPA axis to combined CRF and AVP stimuli in obese women with different obesity phenotypes. Moreover, we examined hormonal and cardiovascular responses to several mental stress tasks, according to previously standardized procedures. Two groups of age-matched premenopausal eumenorrheic obese women with visceral (V-BFD) or subcutaneous (S-BFD) body fat distribution and a group of normal-weight healthy controls were investigated. All women randomly underwent the following protocol: (1) a combined CRF/AVP test (100 micrograms plus 0.3 IU intravenously [IV], respectively); (2) a standardized stress test, which consisted of completing two puzzles and a mental arithmetic test; and (3) a control saline test. Blood samples for ACTH and cortisol determinations were obtained before and during each test, and measurements of arterial blood pressure and pulse rate were made at regular intervals during the stress test. After combined CRF/AVP administration, ACTH and cortisol were significantly higher in V-BFD than in the other two groups. In contrast, no significant hormonal variation was found in either group during stress tasks. During the stress test, pulse rate (but not arterial blood pressure) significantly increased after 8 and 15 minutes in the V-BFD group, whereas no significant variation was found in S-BFD and control women. A significant correlation was present between the pulse rate and change in cortisol level during the stress test at minutes 8 (r=.54, P<.05) and 15 (r=.57, p<.01) in all women considered together. Subjective emotional involvement during stressful tasks was measured by a two-dimensional short verbal scale, which revealed that the stress section had a more significant impact in obese V-BFD than in S-BFD and control women. These data therefore confirm that women with visceral obesity have hyperactivity of the HPA axis, and that the combined CRF/AVP stimulation may offer a good tool for investigating pituitary reserve in this obesity phenotype. Moreover, the results indicate that these women probably have a hyperreactive sympathetic response to acute stress that seems interrelated to that of the HPA axis.

Adrenocorticotropic Hormone↗
PubMed2003

Metabotropic glutamate receptor 5 antagonist-induced stimulation of hypothalamic-pituitary-adrenal axis activity: interaction with serotonergic systems.

The mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP) produces anxiolytic or antidepressant effects in several rodent models through incompletely described mechanisms. Anxiolytics and antidepressants share several neuroendocrine features, including acute activation of the hypothalamic-pituitary-adrenal (HPA)-axis, desensitization of neuroendocrine responses with repeated dosing, and desensitization of the HPA axis to 5-HT1A agonist stimulation. We characterized these neuroendocrine parameters in rats treated systemically with MPEP and compared them to those induced by the anxiolytic buspirone. Acutely, MPEP dose-dependently (0.1-10 mg/kg i.p.) increased plasma corticosterone concentrations. These responses were blocked by 50% with the 5-HT1A antagonist WAY100635. The corticosterone responses to both 3 mg/kg MPEP and buspirone were decreased by 80% after 5 days of twice-daily injections. Repeated injection with MPEP decreased HPA-axis sensitivity to buspirone challenge by 75%. This desensitization was not associated with changes in mGluR5 or 5-HT1A receptor binding properties, expression of G-protein subunits coupled to these receptors, or in 5-HT-stimulated binding of [(3)H]-GTPgammaS to membranes. We conclude that MPEP acutely disinhibits the HPA axis, in part through uncharacterized changes in serotonergic signaling. Desensitization of 5-HT1A responses after repeated MPEP administration may indicate that, like other anxiolytics and antidepressants, plasticity in 5-HT signal transduction pathways has occurred.

Animals↗
PubMed1998

Alignment of the umbilical axis: an effective maneuver for laparoscopic entry in the obese patient.

BACKGROUND: In obese patients, a panniculus may cause a caudal deviation in the vertical axis of the umbilicus and make laparoscopic entry difficult. TECHNIQUE: First, the presence or absence of caudal deviation of the umbilical axis is ascertained by measuring the distance between the external umbilical orifice and the anterior superior iliac spines along the length of the patient. Second, the caudally deviated umbilicus is displaced cranially by manual pressure on the panniculus so that the external umbilical orifice rests approximately 8 cm above the level of the anterior superior iliac spines. Third, open laparoscopy is performed through the base of the umbilicus by elevating it with clamps and incising skin, fascia, and peritoneum in a vertical axis. EXPERIENCE: In an 18-month period, 67 consecutive obese women (weight range 99-213 kg) underwent surgery by the authors for gynecologic conditions requiring primary intraperitoneal evaluation or treatment. All of these patients were scheduled for laparoscopy and underwent the assessment, alignment, and entry technique described above to commence the operations. Laparoscopic entry by this technique was successful and rapid in all 67 cases and was not complicated by preperitoneal insufflation, subcutaneous emphysema, visceral injury, vascular injury, penetration of an underlying skin fold, or postoperative wound complications. CONCLUSION: Umbilical axis assessment and alignment safely facilitates laparoscopy in obese patients.

Adult↗
PubMed2003

Effect of the serotonin agonist buspirone on behaviour and hypothalamic-pituitary-adrenal axis in confident and fearful mink.

Behavioural and hypothalamic-pituitary-adrenal (HPA) axis responses were investigated in farm mink (Mustela vison) selected for either confident or fearful behaviour for nine generations. Two groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given the serotonin (5-HT) 1A receptor agonist buspirone (1.25 mg/kg/day), whereas two other groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given saline, continuously for 5 weeks via osmotic minipumps. Behavioural reactions towards a novel object and towards humans were tested after 19-25 days, and HPA axis reactivity [adrenocorticotropic hormone (ACTH), cortisol] was measured after 28-31 days of treatment. Confident mink were more exploratory than fearful mink towards humans and a novel object. Confident mink spent more time in contact with the object than did fearful mink during saline-but not during buspirone-treatment. buspirone increased approach-withdrawal conflict behaviour towards a object in fearful mink only. The chronic dose of buspirone did not reduce fear towards humans and did not affect latencies to reaction, number of contacts, number and duration of manipulations, and stereotypic behaviour in a Novel Object test. Different HPA axis responses have emerged between confident and fearful mink, together with a different degree of fear-related behaviour. Fearful mink have a higher cortisol combined with a lower ACTH secretion than confident mink in response to capture and blood sampling. The central serotonergic system may be involved, and even though the precise underlying mechanisms are presently unknown, treatment with a 5-HT(1A) receptor agonist reduces the difference between confident and fearful mink in HPA axis reactivity.

Adrenocorticotropic Hormone↗
PubMed2001

The visual consequences of deviations in the orientation of the axis of rotation of the human vestibulo-ocular reflex.

The 3D orientation and amplitude of the movement of each eye evoked by predictable, sinusoidal and non-predictable, sum-of-sines rotation about roll, yaw, pitch and intermediate axes were measured in seven subjects. The rotation axis of the eyes was not always perfectly aligned with the stimulus axis but showed systematic deviations that depended on the orientation of the rotation axis of the head. Misalignment of the oculomotor response with the stimulus axis is equivalent to adding an orthogonal, non-compensatory vector that potentially could introduce retinal slip, rather than compensate for it. The variations in orientation could not be readily explained as an artifact arising from the differential processing of the roll component. Instead, differences in the movements of the left and right eyes had trends appropriate for compensating for the geometrical demands of the translation of the eyes that must necessarily accompany natural head rotation.

Eye Movements↗
PubMed1998

Effect of fluticasone propionate aqueous nasal spray versus oral prednisone on the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Fluticasone propionate is a glucocorticoid with negligible oral bioavailability and very low intranasal bioavailability that is used as an intranasal spray for the treatment of rhinitis. OBJECTIVE: The purpose of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA)axis effects of fluticasone propionate aqueous nasal spray (FP ANS) compared with oral prednisone and placebo by using a 6-hour cosyntropin infusion test. METHODS: In a 4-week, randomized, double-blind, double-dummy, placebo-controlled parallel-group study, 105 adult patients with allergic rhinitis were randomly assigned to receive FP ANS 200 microg once daily, FP ANS 400 microg twice daily, oral prednisone 7.5 mg once daily, oral prednisone 15 mg once daily, or placebo. HPA-axis function was assessed at the screening visit and after 4 weeks of treatment by measuring morning plasma cortisol concentrations and poststimulation concentrations of plasma and urinary cortisol. RESULTS: There was no evidence of altered HPA-axis response to cosyntropin by the end of treatment with FP ANS 200 microg once daily or FP ANS 400 microg twice daily when compared with placebo. In contrast, 4 weeks of treatment with oral prednisone 7.5 or 15 mg once daily was associated with significant (p < 0.05 vs placebo) reduction in HPA-axis function, as evidenced by lower plasma cortisol concentrations (area under the plasma concentration-time curve and peak concentrations) after cosyntropin stimulation and reduced mean 24-hour urinary cortisol excretion. FP ANS 400 microg twice daily and both prednisone regimens were associated with a significant (p < 0.05 vs placebo) reduction in mean morning plasma cortisol concentrations. CONCLUSION: These results indicate that a 4-week course of FP ANS at four times the recommended dose does not suppress adrenal function in response to a 6-hour cosyntropin stimulation test.

Administration, Inhalation↗
PubMed1998

Effects of budesonide by means of the Turbuhaler on the hypothalmic-pituitary-adrenal axis in asthmatic subjects: a dose-response study.

BACKGROUND: As a general phenomenon, corticosteroids may suppress the activity in the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal stimulation test is a commonly used method to assess the relative risk of exogenous corticosteroids to induce systemic side effects. OBJECTIVES: This clinical trial was performed to assess the effects of budesonide on the HPA axis (at 800, 1600, or 3200 microg/day, given as a twice daily regimen, administered by means of the Turbuhaler) in adult patients with mild, non-steroid-dependent asthma. METHODS: Sixty-four asthmatic patients received budesonide or placebo by inhalation or 10 mg/day oral prednisone once daily as a positive control in a double-blind, double-dummy, randomized, placebo-controlled, parallel-group, multicenter study. Plasma cortisol concentration was measured to assess the effect on the HPA axis before and during a 6-hour infusion of synthetic adrenocorticotropic hormone (ACTH), cosyntropin. RESULTS: After 6 weeks of treatment, plasma cortisol concentrations after adrenal stimulation by cosyntropin infusion had fallen by 4% in the placebo group; by 13%, 11%, and 27% in the budesonide groups (800, 1600, and 3200 microg/day, respectively); and by 35% in the prednisone group. The decrease was significant only in the 3200 microg/day budesonide (p = 0.03) and prednisone (p = 0.005) groups. Over the same time period, decreases in basal plasma cortisol concentrations were 1% in the placebo group; 19%, 19%, and 34% in the three budesonide groups; and 37% in the prednisone group. Only in the prednisone group was the decrease significant (p = 0.03 vs placebo). CONCLUSIONS: In this study budesonide inhaled by means of the Turbuhaler, at doses recommended for clinical use (800 or 1600 microg/day), did not produce any statistically significant suppression of the HPA axis compared with placebo.

Administration, Inhalation↗
PubMed1997

The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.

Mutations at the mouse Fused locus have pleiotropic developmental effects, including the formation of axial duplications in homozygous embryos. The product of the Fused locus, Axin, displays similarities to RGS (Regulators of G-Protein Signaling) and Dishevelled proteins. Mutant Fused alleles that cause axial duplications disrupt the major mRNA, suggesting that Axin negatively regulates the response to an axis-inducing signal. Injection of Axin mRNA into Xenopus embryos inhibits dorsal axis formation by interfering with signaling through the Wnt pathway. Furthermore, ventral injection of an Axin mRNA lacking the RGS domain induces an ectopic axis, apparently through a dominant-negative mechanism. Thus, Axin is a novel inhibitor of Wnt signaling and regulates an early step in embryonic axis formation in mammals and amphibians.

Amino Acid Sequence↗
PubMed1998

The left-right coordinator: the role of Vg1 in organizing left-right axis formation.

The asymmetries of internal organs are consistently oriented along the left-right axis in all vertebrates, and perturbations of left-right orientation lead to significant congenital disease. We propose a model in which a "left-right coordinator" interacts with the Spemann organizer to coordinate the evolutionarily conserved three-dimensional asymmetries in the embryo. The Vg1 cell-signaling pathway plays a central role in left-right coordinator function. Antagonists of Vg1 alter left-right development; antagonists of other members of the TGFbeta family do not. Cell-lineage directed expression of Vg1 protein can fully invert the left-right axis (situs inversus), can randomize left-right asymmetries, or can "rescue" a perturbed left-right axis in conjoined twins to normal orientation (situs solitus), indicating that Vg1 can mimic left-right coordinator activity. These are the first molecular manipulations in any vertebrate by which the left-right axis can be reliably controlled.

Activins↗
PubMed1998

Effects of rearing condition on HPA axis response to fluoxetine and desipramine treatment over repeated social separations in young rhesus monkeys.

Normal hypothalamic-pituitary-adrenal (HPA) axis activity is disrupted in several types of human psychiatric disorders, and has been widely reported to be altered as a result of early experience in rodents. In this study the effects of early social experience on later response of the HPA axis to separations from cagemates and pharmacologic treatments were examined in rhesus monkeys. HPA axis activity was measured in mother-reared and peer-reared monkey infants in conjunction with six repeated separations from and reunions with their cagemates. Within each rearing group, infants were assigned to one of three treatment groups that received continuous treatment with either fluoxetine (2 mg/kg), desipramine (DMI, 5 mg/kg) or placebo (saline) beginning 2 weeks prior to separations. At 2 weeks after drug treatment, fluoxetine increased ACTH and cortisol in the treated groups, while DMI decreased ACTH and cortisol in both treated groups; however, these effects were not persistent over the separations. While these treatment effects tended to be more pronounced in the mother-reared group, the rearing groups did not show a clearly differential response to either of the treatments. The most prominent finding was that mother-reared monkeys showed significantly higher ACTH and cortisol levels than peer-reared monkeys over all samples, an effect that may have mitigated a potential rearing group difference in treatment response. The results add to growing evidence for the influence of primate mothers on the functional development of psychobiological systems in their infants, and suggest that the HPA axis is among the more sensitive of these systems to postnatal experience.

Adrenocorticotropic Hormone↗
PubMed2002

Uncoupling of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis in inflammatory bowel disease?

In inflammatory diseases such as Crohn's disease (CD) and ulcerative colitis (UC), one would expect that TNF or IL-6 stimulates the hypothalamus, which activates the hypothalamus-autonomic nervous system (HANS) axis and the hypothalamic-pituitary-adrenal (HPA) axis in a parallel fashion. The study was initiated in order to investigate the parallelism of the HANS and HPA axes. We measured a typical marker of the HANS axis (neuropeptide Y, NPY) and of the HPA axis (serum cortisol). Plasma NPY was positively correlated with serum cortisol in control subjects (R(Rank)=0.259, p=0.026), which is a sign for the parallel activation of the two axes in healthy subjects. However, serum cortisol was not correlated with plasma NPY in CD or UC patients. In the active CD or UC, inclusion of patients with and without prior prednisolone therapy revealed a negative correlation between the serum cortisol and plasma NPY (CD: R(Rank)=-0.285, p<0.05; UC: R(Rank)=-0.510, p<0.01). This study demonstrates that the two stress axes seem to act in a parallel fashion in control subjects but are uncoupled in IBD patients. Uncoupling of these two axes may be partly due to prior corticosteroid therapy, whereas inverse coupling is a result of simultaneous corticosteroid therapy. It is discussed how the uncoupling of the two anti-inflammatory stress axes can appear.

Adult↗
PubMed2002

Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis.

Cytokines, peptide hormones and neurotransmitters, as well as their receptors/ligands, are endogenous to the brain, endocrine and immune systems. These shared ligands and receptors are used as a common chemical language for communication within and between the immune and neuroendocrine systems. Such communication suggests an immunoregulatory role for the brain and a sensory function for the immune system. Interplay between the immune, nervous and endocrine systems is most commonly associated with the pronounced effects of stress on immunity. The hypothalamic-pituitary-adrenal (HPA) axis is the key player in stress responses; it is well established that both external and internal stressors activate the HPA axis. Cytokines are chemical messengers that stimulate the HPA axis when the body is under stress or experiencing an infection. This review discusses current knowledge of cytokine signaling pathways in neuro-immune-endocrine interactions as viewed through the triplet HPA axis. In addition, we elaborate on HPA/cytokine interactions in oxidative stress within the context of nuclear factor-kappaB transcriptional regulation and the role of oxidative markers and related gaseous transmitters.

Animals↗
PubMed2000

Brain oxytocin inhibits the (re)activity of the hypothalamo-pituitary-adrenal axis in male rats: involvement of hypothalamic and limbic brain regions.

In response to various stressors, oxytocin is released not only into blood, but also within hypothalamic and extrahypothalamic limbic brain regions. Here, we describe the involvement of intracerebrally released oxytocin in the regulation of the activity of the hypothalamo-pituitary-adrenal (HPA) axis by infusion of the oxytocin receptor antagonist (des Gly-NH(2) d(CH(2))(5) [Tyr(Me)(2), Thr(4)] OVT; pH 7.4; Dr. M. Manning, Toledo, OH, USA) either into the lateral cerebral ventricle (icv[0.75 microg/5 microl,]) or via retrodialysis (10 microg/ml, 3.3 microl/min, 15 min) into the hypothalamic paraventricular nuclei (PVN), the medio-lateral septum or the amygdala. Male Wistar rats fitted with a chronic jugular vein catheter and an icv guide cannula or a microdialysis probe targeting the respective brain region 4 days prior to the experiment were blood sampled under basal as well as stressful conditions. Rats were exposed to the elevated platform (emotional stressor) and/or to forced swimming (combined physical and emotional stressor). Blockade of the receptor-mediated action of endogenous oxytocin within the PVN resulted in an enhanced basal secretion of ACTH whereas, in response to forced swimming, ACTH secretion was rather reduced, indicating a tonic inhibitory effect of OXT on basal HPA axis activity, but a potentiating action under conditions of stress. Within the medio-lateral septum, antagonist treatment did not alter basal ACTH secretion, but significantly disinhibited ACTH secretion in response to the elevated platform, but not to forced swimming. Within the amygdala, no significant effects either on basal or stress-induced HPA axis activity could be found. The results indicate a differential involvement of brain oxytocin in the regulation of the HPA axis activity which depends both on the site of intracerebral oxytocin release and the stressor the animals are exposed to.

Adrenocorticotropic Hormone↗