Post-menopausal estrogen supplementation only partially blunts the sympathoadrenal response to mental stress.
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Biomedical subjects
Publications and source records attributed to G Ceresini.
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The aim of this study was to investigate the role played by the neuropeptide galanin (GAL) in the regulation of sympathoadrenal function. We evaluated the effects of rat GAL (rGAL) and of the putative GAL receptor antagonist galantide (GLT) on epinephrine (E) and norepinephrine (NE) plasma levels in conscious freely moving male rats, during a psychosocial stress condition. Four groups of male rats were challenged by a stress stimulus, obtained by exposing the animals to a resident conspecific fighter (intruder model), following an intravenous injection with (1) rGAL + saline (SAL), (2) GLT + SAL, (3) rGAL + GLT, or (4) SAL + SAL. Plasma levels of both E and NE were also measured in an additional group of male rats not exposed to any stressor stimulus. The results (mean+/-SEM) showed that rats exposed to the stressor stimulus (intruder rats) exhibited a significant increase above baseline in circulating levels of both E (peak values of 834.13+/-115.13 pmol/l vs. basal values of 309.31+/-32.93 pmol/l; p < 0.01) and NE (peak values of 5,299.03+/-450.62 pmol/l vs. basal values of 2,798.24+/-311.56 pmol/l; p < 0.01) in comparison to control, nonstressed rats. The comparison of the areas under the curve response (AUC) among treatments in the intruder rats revealed that rGAL + SAL injections resulted in a further increase in E levels when compared to SAL + SAL treatment (AUC values: 8.26+/-0.64 vs. 25.38+/-5.52 nmol/ 1/20 min in SAL + SAL vs. rGAL + SAL treatment, respectively; p < 0.02). No significant changes in stress-induced E plasma levels were found following GLT + SAL treatment in comparison to SAL + SAL injections. When the intruder rats were submitted to rGAL + GLT injections, the increments in E levels were found to be higher than those observed following SAL + SAL treatment (AUC values: 8.26+/-0.64 vs. 36.00+/-13.76 nmol/ 1/20 min in SAL + SAL vs. rGAL + GLT treatment, p < 0.03); however, the values were not significantly different from those observed in rGAL + SAL-injected rats. No significant changes in stress-induced NE levels were found in either treatment group when compared to SAL + SAL-injected intruder rats. The results of this study demonstrate that rGAL administration leads to an increase in the E response to the stress stimulus without any effect on NE response. Galantide does not affect either the physiological stress-induced elevation of plasma catecholamines or the effects of rGAL on E plasma levels in response to stress. Therefore, GLT does not appear to behave as a GAL receptor antagonist in the regulation of sympathoadrenal function in rats.
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.
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.
The neuropeptide galanin (GAL) has been shown to be located in the pituitary gland and to modulate the secretion of several pituitary hormones. In the human pituitary, GAL is almost exclusively located within corticotrophs. We examined whether GAL is secreted from corticotrophs in response to stimuli that induce ACTH release. Plasma levels of GAL and ACTH were evaluated in six healthy female subjects in the follicular phase of the menstrual cycle after the following treatments: 1) ovine CRH (oCRH) injection during saline (SAL) infusion, 2) oCRH injection during infusion of the arginine vasopressin analog desmopressin (DP), 3) SAL injection during DP infusion, and 4) SAL injection during SAL infusion. DP (4.3 ng/min.kg BW) or SAL was infused from 0-60 min. oCRH (1 microgram/kg BW) or SAL was administered by a 2-min injection at 5 min. The expected ACTH response to oCRH was enhanced by the concomitant DP administration (peak level, 10.39 +/- 1.12 vs. 21.37 +/- 3.43 pmol/L in SAL infusion plus oCRH injection vs. DP infusion plus oCRH injection, respectively; P < 0.05). The mean integrated ACTH response, expressed as the area under the curve, to SAL infusion plus oCRH injection vs. that to DP infusion plus oCRH injection was 288.23 +/- 61.94 vs. 699.70 +/- 91.80 pmol/L.60 min, respectively (P < 0.05). A slight, but not significant, increase was observed in ACTH values after DP infusion plus SAL injection compared to that after SAL infusion plus SAL injection challenge. Plasma GAL levels were highly variable. No changes in GAL levels were found concomitant to ACTH values in either experimental group. In fact, GAL levels were not significantly affected by either treatment. These data confirm that DP potentiates the ACTH response to CRH in humans. Furthermore, our results suggest that GAL is probably not cosecreted with ACTH in normal subjects. The possibility exists that GAL produced by corticotrophs exerts its action principally through a locally mediated paracrine or autocrine mechanism without being secreted into the bloodstream.
In the medial preoptic area and the diagonal band of Broca, a subset of LHRH neurons coexpresses galanin at a 4- to 5-fold higher rate in female than male rats, suggesting that estradiol (E2) plays a key role in galanin gene expression within LHRH neurons. In the present studies we investigated the incidence of colocalization of these peptides in different age groups, i.e. 2-, 10-, 18-, and 24-month-old intact female Fisher rats; 24-month-old E2-treated rats; 24-month-old ovariectomized (OVX) rats; and 24-month-old OVX E2-treated rats with single or double labeling immunocytochemistry. For cell counting, we took advantage of the typical fusiform morphology of galanin-immunoreactive neurons that colocalize LHRH. The presence of both peptides in the same perikaryon was substantiated by double staining representative sections from each brain. Our observations indicate that the number of galanin/LHRH-coexpressing perikarya dramatically decreased with age. Although in 18-month-old rats a moderate decline was observed, in 24-month-old female rats no, or only a few, faintly stained, fusiform galanin-immunopositive perikarya were present. Although galanin was absent from LHRH neurons of aged rats, their LHRH content was not altered. E2 treatment of intact 24-month-old rats had no effect on the low incidence of colocalization. However, when OVX 24-month-old rats were E2 treated, the incidence of colocalization increased to the level seen in 2- or 10-month-old estrous animals. Our observations on the presence of colocalizing perikarya in intact and E2-treated aged animals provide further evidence for the key role of E2 in galanin gene expression within LHRH neurons and emphasize that some ovarian factor(s) may blunt this effect.
Growth hormone (GH) secretion is decreased during aging in humans and in rodents. This decrease may be due to increased hypothalamic somatostatin release, which is inhibited by cholinergic agonists, or to decreased secretion of GHRH. Alpha-glyceryl-phosphorylcholine (alpha-GFC) is a putative acetylcholine precursor used in the treatment of cognitive disorders in the elderly. In order to learn what effect alpha-GFC had on GH secretion, GH-release hormone (GHRH) was given to young and old human volunteers, with or without the addition of alpha-GFC. GH secretion was greater in the younger subjects than in the old individuals, and both groups had a greater GH response to the GHRH+alpha-GFC than to GHRH alone. The potentiating effect of alpha-GFC on GH secretion was more pronounced in the elderly subjects. These findings confirm the observation that aged individuals respond less well to GHRH than younger subjects, and provides further evidence that increased cholinergic tone enhances GH release.
To investigate the effects of aging on the secretion of the common alpha-subunit of the glycoprotein hormones, we measured basal levels of luteinizing hormone (LH), testosterone (T) and alpha-subunit in 176 normal men aged 19 to 89 years. In addition, in two groups of young (less than 65 years; n = 25) and old (greater than 65 years; n = 15) subjects, the effects of luteinizing hormone-releasing hormone (LHRH) on LH and alpha-subunit secretion were determined. Age-related increases in serum alpha-subunit and LH were noted only in the oldest men while T levels decreased progressively with advancing age. LHRH stimulation resulted in significantly greater secretion of alpha-subunit in the old subjects while no difference in LH release between young and old men was observed. Moreover, there was a delay to peak LH and alpha-subunit levels after LHRH in the old subjects. These data suggest that the aging process in males involves deficits in both testicular and gonadotroph functions as demonstrated by (1) the relative hypogonadotropic hypogonadism seen until the ninth decade; (2) the hypergonadotropic hypogonadism apparent in men greater than 80 years; (3) the delay in the timing of peak responses of LH and alpha-subunit after LHRH administration; and (4) the disproportionate increase in the secretion of alpha subunit relative to intact LH.
The basal and GH-releasing hormone-stimulated secretion of GH declines in the elderly. We tested the ability of cytidine 5'-diphosphocholine, a drug used in the treatment of stroke and Parkinson's disease, to alter GH secretion in 11 healthy elderly volunteers, aged 69-84. Each subject received an iv infusion of 2 g of cytidine 5'-diphosphocholine or normal saline. GHRH and TRH were also administered during cytidine 5'-diphosphocholine infusions. The infusion of cytidine 5'-diphosphocholine induced a 4-fold (p less than 0.05) increase in serum GH levels over basal values. A small increase in GH was seen after GHRH administration. However, the addition of GHRH to the cytidine 5'-diphosphocholine infusion resulted in a GH response which was significantly greater than that seen after GHRH alone; the integrated concentration of GH was more than 2-fold greater in the cytidine 5'-diphosphocholine treated group (706.85 +/- 185.1 vs 248.9 +/- 61.4 micrograms.l-1.(120 min)-1; p = 0.01). The PRL and TSH responses to TRH were not significantly affected by cytidine 5'-diphosphocholine infusion, indicating that dopaminergic mechanisms are not involved. These studies demonstrate that cytidine 5'-diphosphocholine can enhance basal and GHRH-stimulated GH release in the elderly, but the mechanism of action of the drug remains unclear.
Chronic treatment with LHRH analogs is known to depress testosterone (T) values to castration levels. In contrast to results from animal experiments, studies in humans indicate that a pituitary-dependent mechanism predominates in the suppression of plasma T. However, this reduction in T levels may occur when LH values are within or below the normal range. One explanation for this result has been that while absolute values of LH in serum may not change, the bioactivity of LH is reduced. The present study has been performed to determine whether this discrepancy between LH and T values is obscured by the hypersecretion of the alpha-subunit which is devoid of any biological activity but crossreacts in most RIAs with LH. Following 2 days of blood collection to establish basal serum hormone levels, six men with prostatic cancer were treated with the LHRH agonist, Buserelin (500 micrograms sc, daily injection) for 15 days. The most significant endocrine responses at the end of this treatment were as follows: 1) T levels were depressed to the castration range; 2) no change was seen in the LH values with a conventional RIA procedure which crossreacted with the alpha-subunit; 3) a significant decrease was found in the LH values evaluated with an immunoradiometric (IRMA) method, which shows no cross-reactivity with the alpha-subunit; 4) there was a significant increase in the alpha-subunit levels; and 5) serum FSH levels were significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to investigate the regulatory mechanisms involved in the secretion of glycoprotein hormones, we studied the secretory patterns of LH, FSH and alpha-subunit in hypogonadal men. Three groups of patients with carcinoma of the prostate were studied both before and 15 days after orchiectomy, or the initiation of ketoconazole or LHRH analog therapy. There were significant increases (P less than 0.01) in LH and alpha-subunit levels in the patients treated with orchiectomy and ketoconazole, but FSH levels increased only in the orchiectomized patients. After LHRH analog treatment, LH levels were significantly decreased when assayed with an immunoradiometric assay method which does not cross-react with alpha-subunit. FSH values were significantly lower than pretreatment levels, while alpha-subunit levels remained significantly elevated throughout the study period. These results demonstrate that after both chemical (ketoconazole) and surgical castration, the secretion of alpha subunit follows a pattern which is tightly correlated with that of LH but not of FSH. However, after LHRH analog treatment, alpha-subunit appears to be the sole secretory product of the gonadotroph.
Expression of the alpha-subunit of glycoprotein hormones is an acquired feature of the endocrine cells of the oxyntic mucosa in patients with sustained serum levels of gastrin, and may be related to the hyperplasia-carcinoid sequence occurring in these patients. In the present study we have investigated the intragastric cellular localization and the circulating levels of alpha-subunit in a patient with Zollinger-Ellison syndrome. In this patient we have found that: 1) Endocrine cells accounted for 2.29% +/- 1.44% of the total oxyntic mucosal volume (normal value: 0.9% +/- 0.4%), with the ECL cells representing 63.22% +/- 10.9% of the total endocrine cell volume (normal value: 29.8 +/- 8.8%). 2) Cells immunoreactive for the alpha-subunit were found to correspond ultrastructurally to a subpopulation of enterochromaffin-like cells, indistinguishable from similar cells devoid of significant immuno-electron microscopic labeling. 3) Immunoreactive cells included a portion of oxyntic endocrine cells with punctate granules, a feature previously observed only in carcinoid tumors of the oxyntic mucosa. 4) In consecutive sections of freeze-dried vapor-fixed biopsies a fraction of alpha-subunit storing cells was found to co-express histamine. 5) The serum alpha-subunit levels were abnormally elevated and paralleled those of gastrin in a secretin-stimulation test. Analysis of similar curves in two other patients with Zollinger-Ellison syndrome, and five patients with hypergastrinemic atrophic gastritis, all presenting alpha-subunit containing oxyntic endocrine cells, showed significant alpha-subunit elevations only in the patients with ulcerogenic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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Calcitonin has been shown to modulate pituitary hormone secretion in a variety of ways. In this study we examined the effects of a salmon calcitonin infusion on GHRH-induced GH secretion in 5 normal men. In addition, in vitro experiments were performed using primary cultures of rat anterior pituitary cells in order to examine whether there is a direct pituitary effect of CT. Infusion of CT significantly blunted the GH response to GHRH in all subjects without affecting basal GH secretion or plasma calcium levels. Infusion of CT was accompanied by significant increases in ACTH, beta-endorphin, cortisol and free fatty acid levels, and by a significant decrease in serum insulin levels. The addition of CT to primary cultures of rat pituitary cells did not alter basal or stimulated secretion of GH or ACTH. These results indicate that: 1) CT blunts the GH response to GHRH; 2) CT infusion results in the stimulation of the hypothalamic-pituitary-adrenal axis, and 3) this effect is probably exerted at the hypothalamic level, since no direct activity of CT was documented in vitro on either GH or ACTH secretion.
The study was designed to assess glycaemic homeostasis in different situations of chronic stimulation of the opiate receptors by exogenous opiates. After an OGTT, levels of glycosylated haemoglobin (HbA1c) and serum fructosamine were measured in 3 groups of male drug addicts of comparable age. Group A consisted of 10 subjects undergoing substitution treatment with oral methadone. Group B consisted of 10 subjects addicted to intravenous injection of the syrup based methadone intended for oral administration. Group C consisted of 10 heroin addicts. Ten healthy subjects of the same age and sex were used as controls. Analysis of the results showed normal glucose tolerance in all groups with tendentially higher basal glycaemia levels in group B. HbA1c levels were significantly higher, though within normal limits, in group B than in either those receiving oral methadone (p less than 0.01) or the heroin addicts (p less than 0.01). The group B subjects also showed the highest fructosamine levels that were both well above normal limits and higher than those in the other groups in whom fructosamine levels were normal. The data therefore confirm normal glycaemia compensation in those taking oral methadone and in heroin addicts during the period considered. A new type of drug addiction involving the intravenous injection of methadone was also encountered. This produces an outstanding short-term change in glycaemic homeostasis and may well lead to future alterations in glucose tolerance.
Diabetes insipidus is a well-known complication of hypophyseal surgery. The case is described of a women presenting with evident polyuropolydipsic syndrome arising 9 years after transphenoidal hypophyseal adenectomy. The diagnosis insipidus diabetes was secondary to intrasellar scars revealed by a hypophyseal CAT scan. The unusually long interval between surgery and the onset of the syndrome is emphasised.
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