Neuroendocrine responses to psychological stress in adolescents with anxiety disorder.

Neurotransmitter-neuroendocrine and cardiovascular responses to the administration of a psychologically stressful mixed-model test (Mental Arithmetic, Stroop Color Word Interference Task, Trier Social Stress Test) were examined in 20 male peripubertal subjects affected by anxiety disorder (group A: 14 with generalized anxiety disorder, 6 with generalized anxiety disorder and separation anxiety disorder) and 20 junior school adolescents, matched for age, without overt psychological disorders (group B). Plasma levels of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EP), cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (Te) were measured immediately before the beginning of the tests and 30 min later at their end. Mean prestress values of GH, PRL, beta-EP and ACTH were significantly higher in anxious subjects than in controls. There was no difference in NE, EPI, CORT and Te prestress levels in the two groups. After the psychological stress session NE, GH and Te concentrations increased significantly in anxious subjects (A), but not in controls. In contrast, beta-EP and PRL decreased significantly during the psychological stress session in anxious subjects, and were unaffected by stress in the subjects without anxiety. No significant changes were found in ACTH, CORT and EPI during the challenge either in anxious subjects or in controls, which may be attributed to the late time of poststress blood sampling. In contrast to controls, heart rate and systolic blood pressure increased significantly in anxious subjects after psychological stress testing. Our data support the hypothesis that the hyperactivity of the noradrenergic system in response to stress is associated with anxiety disorders in adolescents and might influence the responses of GH and Te. High prestress basal values of stress hormones seem to be induced in anxious subjects by the anticipation of the task or by a persistent hyperactivity of the noradrenergic system. Further studies are needed to investigate in more detail the involvement of the HPA axis in anxious adolescents by a more refined resolution of time points of blood sampling.

Neuroendocrine responses of healthy volunteers to 'techno-music': relationships with personality traits and emotional state.

A variety of studies reported psychological and physiological effects of music. Different types of music have been found to induce different neuroendocrine changes. The aim of the present experiment was to investigate the possible combination of emotional and endocrine changes in response to techno-music and to define personality variables as predictors of respective changes. Sixteen psychosomatically healthy subjects (18- to 19-year-olds, eight males and eight females) were exposed, in random order, to techno-music or to classical music (30 min each). Plasma norepinephrine (NE), epinephrine (EPI), growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH) cortisol (CORT), beta-endorphin (beta-EP) concentrations and changes of emotional state were measured in basal conditions and after the experimental trials with two different types of music. Techno-music was associated with a significant increase in heart rate, systolic blood pressure and significant changes in self-rated emotional states. A significant increase was observed in beta-EP, ACTH, NE, GH and CORT after listening to techno-music. Classical music induced an improvement in emotional state, but no significant changes in hormonal concentrations. No differences between male and female subjects' responses to music have been found. Plasma levels of PRL and EPI were unaffected by techno- and classical music. Changes in emotional state and NE, beta-EP and GH responses to techno-music correlated negatively with harm avoidance scores and positively with the novelty-seeking temperament score on the Cloninger scale. Listening to techno-music induces changes in neurotransmitters, peptides and hormonal reactions, related to mental state and emotional involvement: personality traits and temperament may influence the wide inter-individual variability in response to music.

Evaluation of circulating galanin levels after exercise-induced pituitary hormone secretion in man.

The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems, anterior pituitary, and adrenal medulla. GAL is colocalized with corticotropin (ACTH) in the human pituitary and with epinephrine (E) and norepinephrine (NE) in chromaffin cells of the adrenal medulla. The function of GAL in peripheral tissues is not known, although the presence of the peptide in corticotrophs and the adrenal gland suggest that it participates in stress responses. In the present study, we investigated whether GAL is cosecreted with ACTH during activation of corticotrophs by an acute physical exercise test. Circulating levels of GAL and pituitary hormones were measured in healthy exercise-tested and control male subjects. Blood samples were collected during basal conditions, maximal power output (MPO), and the recovery period. Control subjects were sampled during the resting condition. The pituitary response to exercise was characterized by a significant increase in ACTH plasma levels (peak value 13.28 +/- 2.19 v 6.68 +/- 1.01 pmol/L, P < .05) and growth hormone (GH) serum levels (peak value, 14.53 +/- 5.59 v 0.29 +/- 0.1 microg/L, P < .02), with the peak in hormone levels detected 15 minutes after the end of exercise. No change in circulating prolactin (PRL) levels was detected. An expected significant increase in plasma levels of both E (peak value, 1,574.41 +/- 403.31 v 267.44 +/- 60.03 pmol/L, P < .01) and NE (peak value, 7,275.25 +/- 955.80 v 961.51 +/- 168.40 pmol/L, P < .01) was also observed. Plasma GAL levels were not affected by the acute exercise test, with the levels being comparable to baseline during the exercise test and the recovery phase. At any sample time, GAL values were comparable between exercise-tested and control subjects. These data show that despite the colocalization of GAL and ACTH within the same pituitary cells, the two peptides are not coreleased in response to stress resulting from acute physical exercise. Furthermore, pituitary GAL seems not to be involved in the stimulation of GH secretion in exercise-tested subjects. The results also indicate that GAL is not coreleased with E or NE in response to the exercise-induced stress condition.

Concomitant evaluation of plasma galanin and catecholamine levels during a cold pressor test in healthy human male and female subjects.

The neuropeptide galanin (GAL) is localized in the peripheral and central nervous systems as well as in the adrenal medulla where it coexists with catecholamines. We evaluated the changes in GAL plasma levels as well as systolic and diastolic blood pressures and in the plasma levels of epinephrine and norepinephrine (NE) in normal human male and regularly menstruating female subjects during the activation of the sympathoadrenal system by a cold pressor test. The test was performed by immersing the hand of the subject in 1 degree C cold water for 4 min. Blood samples were collected both under basal conditions and at subsequent intervals during the cold stimulus as well as at the end of the recovery phase. The values were compared with those obtained when the same subjects were sham tested. As expected, systolic and diastolic blood pressures increased in both sexes during the cold test; the systolic blood pressure values were significantly (p < 0.05) higher in males. Epinephrine and NE levels rose significantly above baseline in both male and female subjects after the cold stimulus; the NE increments were significantly (p < 0.05) higher in males. The basal GAL levels were found to be variable but not sexually dimorphic. In both sexes, during cold stimulus and recovery phase, GAL values were found to be not significantly different from those detected during the sham test. These results demonstrate that the release of GAL in peripheral blood is not associated with that of catecholamines in response to the cold pressor test.

Neuroendocrine responses to emotional arousal in normal women.

The neuroendocrine effects of many stressful challenges and experimentally induced emotional states have been investigated in humans, but few data are available concerning the psychobiological correlates of the emotional arousal induced by TV violence, fear and conflictual emotions. In this study we evaluated cardiovascular, hormonal and mood changes induced by the view of a violent or, in random order, neutral movie in 20 healthy young women. The emotional arousal was associated with a significant increase in heart rate, systolic blood pressure and significant changes in self-evaluated mood states. beta-Endorphin, adrenocorticotrophic hormone, epinephrine and growth hormone showed a significant increase during emotional arousal, with a significant interaction mood-time. Cortisol increased significantly during the violent movie (areas under curves analysis), but not significant interaction mood-time has been demonstrated. Prolactin and norepinephrine levels did not show a significant change during the emotional stimulus. Our data evidence the existence of neuroendocrine changes associated with the defence mechanism and aroused by movie violence and conflictual situations.

Noradrenergic and hormonal responses to physical exercise in adolescents. Relationship to anxiety and tolerance to frustration.

Seventy physically healthy 14-year-old adolescents, 40 boys and 30 girls, were evaluated psychologically and endocrinologically. After the psychological tests (Anxiety Score Test for Adolescents, Rosenzweig, Pictures Frustration Test for Children), subjects were divided into group A, with low anxiety/sense of guilt and high self-esteem/tolerance to frustration and group B with the opposite. In both groups, we measured basal plasma levels of noradrenaline (NE), growth hormone (GH), prolactin (PRL), melatonin (MT) and luteinizing hormone (LH) and their response to physical exercise (the Harvard step test). Basal levels of the hormones and of NE were not different in the two groups. After the physical stimulus, NE levels rose significantly more in B girls than in A and significantly less in B than in A boys. GH and PRL levels increased only in A girls and MT in B boys, while LH levels decreased in A boys and girls but not in B subjects.

Tissue polyamine concentrations in the European sea bass (Dicentrarchus labrax L.): change with age and season of the year.

Independently of the age of the European sea bass, putrescine and spermidine are much higher in liver and brain than in muscles, while spermine concentrations are more similar to one another. The polyamine concentrations are higher in 2 years old sea bass than in 1 year old fish except for heart spermidine and liver spermine. Lowering in water temperature causes a decrease in the concentration of spermidine and spermine in all tissues examined. Putrescine, however, increases in heart, caudal muscle, liver and brain and it is unchanged in red and dorsal muscles.

Effect of GnRH administration on blood polyamines and LH levels in normal and obese children.

Blood polyamines (spermidine and spermine) and LH levels have been studied after acute GnRH injection both in obese and normal weight children. In both groups LH values significantly increased after stimulation but reached higher peaks in normal children than in obese ones (P less than 0.05). On the contrary, polyamine levels increased significantly only in the normal weight children. LH peaked at 30 min and polyamines at 60 min after GnRH injection. On the basis of the proposed role of polyamines in hormone action and of our results, we suggest that polyamines may play a pivotal role in hormone responsiveness of hypothalamic-hypophyseal axis.

Changes of polyamine concentrations in infants during the first six months of life.

Polyamines were detected in the blood of infants during the first six months of life. The highest spermidine levels were found at the 2nd and the 4th month after birth. Spermine, on the contrary, does not show significant differences. Different types of diet produced no changes in the polyamine pattern.

A possible role for polyamines in cartilage in the mechanism of calcification.

The role of polyamines in cartilage is not known: they may be somehow related to the mechanism of calcification. In epiphyseal cartilage from calf scapulas, they are more concentrated in the ossifying area, where calcification takes place, than in the resting region. Spermidine is present in greater amounts than spermine and putrescine. Since ornithine decarboxylase (EC 4.1.1.17) is measurable only in the resting region of the tissue, it is in this area that polyamine biosynthesis occurs, while they accumulate in the ossifying area. Immunohistochemical evidence is obtained that only in the ossifying zone is spermidine extracellular. It is at this level that the matrix is rearranged to become calcified, and proteoglycans are dissociated and partially removed. The effect of polyamines on solutions of proteoglycan subunits has been studied in vitro by following variations of turbidity and viscosity. While in the presence of putrescine the specific viscosity decreases to asymptotic values, in the presence of either 30 mM spermidine or 2.5-10 mM spermine, the decrement is more marked. At the same concentrations, increase of the turbidity of proteoglycan subunit solutions was observed. Only spermidine showed the capacity of displacing proteoglycan subunits from a column of Sepharose 4B-type II collagen: at 15 mM concentration, about 90% of proteoglycans were removed from the column. Alkaline phosphatase activity, which plays an important role in calcification, is enhanced by spermidine and spermine. These results obtained in vitro support the hypothesis that polyamines may be related to calcification of preosseous cartilage.

Pattern of human blood spermidine and spermine in prematurity.

Blood polyamines have been determined in preterm newborns (24-37 gestation weeks) during the first hours of life and until 20 days after birth. The most elevated polyamine concentrations were found in preterm newborns from the 24th-33rd gestational week. In all preterms, however, polyamine concentrations are higher than in full term newborns. In preterm infants two different patterns of blood polyamines appear in relation to the gestational age: in infants born at 24-34 wk, spermidine reaches the peak at 12 h and spermine shows high concentrations between 12 and 48 h. In infants born at 35-37 wk maximal concentrations of polyamines were reached at 12 h. Successively, in both groups the polyamines progressively decrease up to the 20th day, with some individual variations. Our results may provide a further support to the suggestion of a fetal genesis of polyamines and their involvement in fetal growth.

Pattern of blood polyamines in healthy subjects from infancy to the adult age.

Blood polyamine levels have been determined in 161 healthy subjects from newborn to adult age. During the growth period spermidine concentrations are always higher than in adulthood. In the first days of life a typical pattern for spermidine and spermine appeared with an early increase in the first hours after birth and a maximum at 24 h; afterwards the levels of both amines gradually and progressively decreased. The levels reached by 10 days of life were maintained until adulthood, at which time a further decrease was evident. The high levels of polyamines during the period of body growth may suggest that also in humans these substances play a role in the process of cellular proliferation.

Effects of human growth hormone on blood polyamines in hypopituitarism.

Blood levels of polyamines were evaluated in hypopituitary patients after i.m. injection of human growth hormone (hGH). After hGH administration polyamine concentration increased significantly in the first 60 minutes. The concentration of spermidine and spermine increases more in patients previously untreated or treated intermittently with hGH than in patients under continuous treatment. The results suggest that in human as well as in experimental models, polyamines could be involved in the growth process and that hGH probably stimulates polyamine synthesis.

[Concentrations of polyamines in maternal and umbilical-cord blood and in the amniotic fluid during normal human pregnancy and in feto-placental insufficiency]. / Concentrazioni di poliamine nel sangue materno e funicolare, a nel liquido amniotico durante la gravidanza umana normale e l'insufficienza feto-placentare.

Blood maternal polyamines during normal pregnancy exhibit an important augmentation around the 10th and the 34th-38th week, and a minor increase between the 20th-25th week of pregnancy. These peaks coincide with extremely important metabolic events in the feto-placental unit such as maximal growth rate in the placenta and fetus, respectively. The levels of polyamines measured from the 38th to 41th week in the blood of the umbilical cord are higher than in the blood of the mother. Putrescine, spermidine and spermine are not detectable when measured in the non-hydrolized amniotic fluid during normal pregnancy, instead a band with a lower Rf than spermine is present. In case of feto-placental insufficiency polyamine concentration in maternal blood are well below the normal values, from the 34th to 38th week of pregnancy. Such a behaviour appears for umbilical cord blood at the 38th and 39th week. Also the unknown polyamine of the amniotic fluid undergoes evident modification in feto-placental insufficiency. These results show that blood polyamines of the mother are probably of fetal origin, and that modified pattern of maternal polyamines may indicate an insufficient body growth of the fetus.

[Serial evaluation of blood polyamines in children treated with growth hormone]. / Valutazione seriata delle poliamine ematiche in bambini trattati con l'ormone della crescita.

Blood polyamines were evaluated in normal children of various ages (from infancy to adolescence). Polyamines show a distinctive pattern: maximal values were observed during infancy; they decrease during childhood and again increase at puberty. After i.m. injection of Human Growth Hormone (HGH), polyamine concentrations increase significantly in the first 60 minutes. Polyamines increase more in patients previously untreated or treated intermittently with HGH than in patients under continuous treatment. The results suggest that in humans as well as in animals, polyamines could be involved in the growth processes and that the effect of HGH probably consists in a stimulation of polyamine synthesis.

Modifications of major aspects of myocardial ribonucleic acid metabolism as a response to noradrenaline. Action of the hormone on cytoplasmic processing of ribonucleic acid after reserpine treatment.

Treatment of perfused rabbit heart with reserpine causes a decrease of incorporation of labelled precursors into RNA species of subcellular fractions and polyamines. Ornithine decarboxylase, S-adenosylmethionine decarboxylase and cytoplasmic Mn2+-stimulated polyadenylate polymerase activities are not modified. Addition of noradrenaline to reserpine-treated perfused hearts enhances, compared with the control, the incorporation of precursor into RNA in all subcellular fractions other than the nuclear one, restores incorporation of labelled putrescine into polyamines, enhances ornithine decarboxylase and S-adenosylmethionine decarboxylase activities and causes a 12-fold increase in cytoplasmic Mn2+-dependent polyadenylate polymerase activity. After treatment with noradrenaline the increase in radioactivity was found solely in AMP after hydrolysis of microsomal RNA to nucleoside monophosphates.

Modifications of major aspects of myocardial ribonucleic acid metabolism as a response to noradrenaline. Behaviour of polyadenylate polymerase and ribonucleic acid polymerase, acetylation of histones and rate of synthesis of polyamines.

Noradrenaline added to perfused rabbit heart previously perfused with labelled precursors causes, after 2.5 and 5.0 min, a general increase of specific radioactivity or RNA in subcellular fractions, but no augmentation of acetylation of F2a2 and F2a1 histone fractions and no stimulation of DNA-dependent RNA polymerase activities. Synthesis of spermidine and spermine is enhanced at 10.0 min of treatment, when there is also a fall in specific radioactivity of RNA. The cytoplasmic Mn2+-stimulated polyadenylate polymerase activity is strongly enhanced 30s to 2.5 min after injection of noradrenaline or of dibutyryl cyclic AMP. Both the cyclic nucleotide and noradrenaline have no influence in vitro on the polyadenylate polymerase reaction.