Jana Jurčovičová

ACTH and corticosterone response to naloxone and morphine in normal, hypophysectomized and dexamethasone-treated rats.

The effect of opiate receptors blocker naloxone on ACTH and corticosterone secretion in normal, dexamethasone-treated and hypophysectomized rats was studied. A dose-related increase in plasma corticosterone level was found at 45 min after s.c. injection of naloxone in a dose range of 0.25-2.0 mg kg-1. The rise in plasma corticosterone was preceded by a slight increase in plasma ACTH. Acute morphine administration in a relatively low dose (6 mg kg-1 s.c.) induced a significant rise in both plasma ACTH and corticosterone levels. Dexamethasone treatment was followed by low basal corticosterone level, by total inhibition of the stress response and response to morphine injection, while the response to ACTH administration was normal. Under these circumstances as well as in rats 6 days after hypophysectomy, naloxone failed to increase plasma corticosterone levels. It is concluded that a direct stimulation of corticosteroid biosynthesis in adrenal cortex is not involved in the mechanism of naloxone-induced activation of pituitary-adrenocortical function.

Combined restraint and cold stress in rats: effects on memory processing in passive avoidance task and on plasma levels of ACTH and corticosterone.

The effect of restraint stress combined with water immersion (IMO+C), applied at various intervals before and after the acquisition of a passive avoidance task, was studied in rats. The procedure started with two pre-training trials. On the single training trial the rats received a footshock (0.3 mA, 3s) after they entered the preferred dark compartment. The exposure to IMO+C lasting 1 h terminated 4 or 1 h before application of the footshock or started immediately or 3 h after this aversive stimulus. Retention tests were performed 1 and 2 days after the acquisition trial. In an attempt to relate the behavioural responses to the stressor with plasma levels of two stress hormones we measured ACTH and corticosterone under similar conditions as were used in the behavioural experiments. IMO+C exposure terminating 1 h before the training resulted in very short avoidance latencies during retention testing. A similar impairment of retention test performance was found in animals exposed to the stressor immediately after training. When IMO+C exposure terminated 4 h before training the stressed rats exhibited comparably long avoidance latencies as shown by the controls. IMO+C presented 3 h after acquisition trial also did not influence retention of avoidance learning. The hormones were estimated 1 and 4 h after IMO+C, both in the absence and presence of footshock. Both ACTH and corticosterone were significantly increased 1 h after IMO+C termination, and their plasma levels returned to control values within 4 h. Footshock alone increased plasma corticosterone, however, the hormone levels were significantly lower than those estimated after IMO+C terminating 1 h before blood collection. Footshock substantially increased ACTH levels in rats exposed to IMO+C 1 h before footshock, but not in stressed rats with already high levels of corticosterone. In conclusion, IMO+C represents a strong stress stimulus exerting amnesic effect when applied shortly before or after the acquisition trial. Further, the findings indicate the restraint and cold stressor to interfere with consolidation of passive avoidance response. We suggest that the moderate circulating levels of corticosterone found after footshock may be positively related to the memory consolidation, while the exceedingly high levels have an opposite effect.

Increase in plasma ACTH after dopaminergic stimulation in rats

The effects of a dopaminergic agonist, apomorphine, and a dopaminergic antagonist, haloperidol, on plasma ACTH, and corticosterone levels were evaluated in adult male rats. Subcutaneous administration of apomorphine in the dose range of 50–500 μg · kg−1 significantly increased plasma corticosterone levels. Acute treatment with apomorphine (250 μg · kg−1) resulted in an elevation of plasma ACTH concentration, peak values being reached 15 min after the injection. The apomorphine-induced rise in plasma ACTH levels was completely inhibited by pretreatment with haloperidol (1 mg · kg−1). A stimulatory role for dopamine receptors in the control of pituitary ACTH release in the rat is suggested.

Alpha-adrenergic control of growth hormone release during surgical stress in man

The mechanisms involved in the initial release of growth hormone (GH) during cholecystectomy have been studied after the administration of phentolamine in saline and in isotonic glucose, and after the administration of 10% glucose. Infusion of these substances was started 10 min before and terminated 30 min after skin incision. The serum GH levels 30 min after skin incision in a nontreated control group were raised to 14.4 +/- 1.0 ng/ml. The alpha-adrenergic blockade by phentolamine (20 mg during 40 min) regardless of whether administered in saline or in isotonic glucose inhibited GH response to surgery (4.3 +/- 2.1 ng/ml, or 2.2 +/- 0.4 ng/ml). The administration of 10% glucose (40 g during 40 min) led to a diminished response in some, but not in all the patients (6.2 +/- 1.2 ng/ml). It is concluded that the alpha-adrenergic mechanism participates in GH response to surgery.

Treatment of adjuvant-induced arthritis with the combination of methotrexate and probiotic bacteria Escherichia coli O83 (Colinfant).

A certain relationship was observed between the gastrointestinal system, arthritis and immune system. Patients with rheumatoid arthritis have an altered microflora composition and disturbed intestinal defensive barrier. Effect of probiotic bacteria (Colinfant®; COL) with known favorable effect on intestinal microflora was determined on the methotrexate (MTX) treatment of adjuvant arthritis. Rats with adjuvant arthritis were administered methotrexate 0.5 mg/kg body mass 2-times weekly per os, COL 1 mL/kg body mass every second day per os, and a combination of MTX+COL for a period of 28 d from the immunization. Levels of serum albumin, body mass, changes in hind paw swelling, and arthrogram score were estimated in rats as variables of inflammation and destructive arthritis-associated changes. Treatment with MTX, as well as with the combination treatment with MTX+COL significantly inhibited both inflammation and destructive arthritis-associated changes. The combination treatment inhibited both the hind paw swelling and arthrogram score more remarkably than MTX alone; on the other hand, the difference between combination treatment and MTX alone was not significant. Treatment with COL alone had no effect on adjuvant arthritis in rats. Colinfant® can increase the preventive effect of MTX treatment in rat adjuvant arthritis by improving its antiarthritic effects.

Evidence for daily rhythms of the expression of proopiomelanocortin, interleukin-1-beta and interleukin-6 in adenopituitaries of male long-evans rats: effect of adjuvant arthritis.

Objective: Several interleukins (ILs) including IL-1β and IL-6 are produced in the anterior pituitary (AP) where they probably participate in the local regulation of hormone production. Immune challenge brings about the dysregulation of immune-endocrine interaction and enhanced the expression of pituitary IL-1β and IL-6. Little is known about regulation of their production, and therefore the purpose of the present work was to describe the relationship between circulating corticosterone and the mRNA expression of proopiomelanocortin (POMC), IL-1β and IL-6 in the AP during a 24-hour cycle in normal rats and rats with acute adjuvant arthritis (AA). Methods: Groups of intact male Long-Evans rats and rats 23 days after induction of AA kept on a 12-hour light/dark cycle (light on at 6:00 a.m.) were killed at 4-hour intervals starting at 2:00 p.m. Trunk blood was used for corticosterone determination by radioimmunoassay. Adenopituitaries were extracted for total RNA and the message of interest was quantitated by real-time PCR using specific primers and TaqMan probes. Parameters of rhythms were evaluated by cosinor analysis. Results: In normal rats, serum corticosterone showed a circadian rhythm with the peak at 6:00 p.m. and the nadir in the morning hours (p < 0.001). POMC mRNA in AP also showed a circadian rhythm (p < 0.05) which was inversely related to corticosterone levels. IL-1β and IL-6 expression in normal rats showed clear-cut daily rhythms (p < 0.001) with the nadirs in the dark period, in contrast to the corticosterone peak in plasma. In arthritic rats, rhythmic corticosterone secretion was suppressed with a plateau pattern of the rhythm. The mean POMC expression was higher than in controls, and the rhythm failed to be significant. IL-1β expression was suppressed by AA (p < 0.001) but the rhythm was still present (p < 0.05). The rhythmic pattern of IL-6 expression was similar to that of controls, but with higher mesor values (p < 0.05). Conclusion: These results suggest a regulatory relationship between circulating corticosterone and the expression of POMC, IL-1β and IL-6 in AP of normal rats. Arthritis induced a higher expression of POMC and IL-6 in the AP and a suppression of IL-1β mRNA during the 24-hour cycle which suggests the involvement of different regulatory mechanisms compared to normal conditions.

Rat Strain Differences in Responses of Plasma Prolactin and PRL mRNA Expression After Acute Amphetamine Treatment or Restraint Stress

Abstract1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment and restraint stress on plasma level of prolactin (PRL) and PRL mRNA expression in the adenohypophysis in Sprague–Dawley and Lewis male rats, the latter known to have a deficient hypothalamo–pituitary-adrenal (HPA) axis.2. Both restraint stress and AMPH treatment (i.p. in a dose of 8 mg/kg of b.w.) were applied 15 or 30 min before termination of the experiment. Plasma PRL and corticosterone (CORT) were determined by radioimmunoassay. PRL mRNA expression was estimated by a dot-blot hybridization.3. Restraint stress and AMPH treatment induced a significant increase in theCORT plasma level, as an indicator of stress response. Compared to Sprague–Dawley rats, the magnitude of CORT increase after both stimuli was significantly lower in Lewis rats.4. Although restraint stress significantly increased the PRL plasma levels in both rat strains, AMPH treatment reduced the PRL levels in both rat strains. However, the changes of PRL plasma levels had another pattern in Lewis rats than in Sprague–Dawley rats. Control plasma PRL levels were significantly higher in Lewis rats, and in this rat strain AMPH treatment for 30 min increased the PRL levels as compared to the values obtained after AMPH treatment for 15 min.5. Expression of PRL mRNA in adenohypophysis by restraint stress and AMPH treatment had a similar pattern. After a 15-min lasting restraint stress, the expression of PRL mRNA was decreased insignificantly in both rat strains. AMPH treatment induced in Sprague–Dawley rats a significant decrease of PRL mRNA after a 15-min interval while after 30 min there was a significant increase. However, in Lewis rats AMPH failed to significantly change PRL mRNA.6. The results from the present study indicate that the mechanisms mediatingthe effects of acute restraint stress and acute AMPH treatment differ in PRL response in Sprague–Dawley and Lewis male rat strains. Differences in the observed responses in Lewis rats could be related to the deficient activity of HPA axis in this rat strain.

Daily Profiles of Plasma Prolactin (PRL), Growth Hormone (GH), Insulin‐Like Growth Factor‐1 (IGF‐1), Luteinizing Hormone (LH), Testosterone, and Melatonin, and of Pituitary PRL mRNA and GH mRNA in Male Long Evans Rats in Acute Phase of Adjuvant Arthritis

We studied the effects of adjuvant arthritis (AA) on the endocrine circadian rhythms of plasma prolactin (PRL), growth hormone (GH), insulin‐like growth factor‐1 (IGF‐1), luteinizing hormone (LH), testosterone, and melatonin and of pituitary PRL and GH mRNA in male Long Evans rats. Groups of control and AA rats (studied 23 days after AA induction) that were housed under a 12/12 h light/dark cycle (light on at 06:00 h) were killed at 4 h intervals starting at 14:00 h. Cosinor analysis revealed a significant 12 h rhythm in PRL and PRL mRNA (p < 0.001) in controls with peaks at 14:00 h and 02:00 h, respectively. The peak at 02:00 h was abolished in the AA group resulting in a significant 24 h rhythm in parallel with that of PRL (p < 0.05) and PRL mRNA (p < 0.0001). Growth hormone showed no rhythm, but a significant rhythm of GH mRNA was present in both groups (p < 0.0001). Insulin‐like growth factor‐1 showed a 24 h rhythm in control but not in AA rats. The mean values of GH, GH mRNA, and IGF‐1 were significantly reduced in AA. Luteinizing hormone displayed a significant 24 h rhythm (p < 0.01) peaking in the dark period in the control but not AA group. Testosterone showed in phase temporal changes of LH levels with AA abolishing the 02:00 h peak. Melatonin exhibited a significant 24 h rhythm in control (p < 0.001) and AA (p < 0.01) rats with maximum levels during the dark phase; the mesor value was higher in the AA males. These results demonstrate that AA interferes with the rhythms of all the studied hormones except the non‐24 h (arrhythmic) GH secretion pattern and the rhythm in melatonin. The persistence of a distinct melatonin rhythm in AA suggests the observed disturbances of hormonal rhythms in this condition do not occur at the level of the pineal gland.

Increased glucagon secretion during hyperthermia in a sauna

SummaryPlasma glucagon, adrenaline, noradrenaline, insulin and glucose concentrations were measured in 7 healthy young males during hyperthermia in a sauna bath: plasma glucagon levels increased from baseline values of 127.0±12.9 (SEM) pg · ml−1 to a maximum of 173.6±16.1 (SEM) pg · ml−1 at the 20th min of exposure. No change in plasma insulin and a slight increase in plasma glucose concentration were seen. Since a concomitant moderate increase in plasma catecholamine levels was also present, the adrenergic stimulus is believed to trigger glucagon release during hyperthermia. Diminished visceral blood flow, known to occur in sauna baths, may cause a decrease in the degradation of plasma glucagon and thus contribute to the elevated plasma glucagon levels.

Effect of Electroconvulsive Therapy without Anticonvulsive Premedication on Serum Growth Hormone in Man

Serum concentrations of human growth hormone (HGH) were measured in psychiatric patients during the first, third and sixth electroconvulsive therapy (ECT) without anticonvulsive premedication. Serum HGH increased 30 min after the application of current and no differences were found between responses to 1st, 3rd, or 6th ECT. Maximal increase of serum glucose was seen after the first ECT and gradual decreases after the 3rd and 6th ECT were observed