Adrenocorticotropic regulations after bilateral lesions of the paraventricular or supraoptic nuclei and in Brattleboro rats.
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Adrenocorticotropic Hormone↗
Biomedical subjects
G Ixart
Publications and source records attributed to G Ixart.
Effects of raphe lesions on circadian ACTH, corticosterone and motor activity rhythms in free-running blinded rats.
Blinded female rats underwent additional midbrain raphe lesions, in order to explore the role of the raphe in the organization of endogenous circadian rhythms for ACTH, corticosterone (B) and motor activity (MA). Amplitudes and mean levels of rhythms were depressed for ACTH and MA, with persistent free-running circadian periodicity for MA and, in several rats, for ACTH and B as well. Other rats exhibited split circadian and ultradian rhythmicity for ACTH and B, whereas other again displayed no detectable ACTH rhythmicity. These results are discussed in the light of the structure of circadian pacemaker systems.
Adrenocorticotropic Hormone↗
[Effects of the destruction of the suprachiasmatic nuclei on the circadian rhythms of ACTH corticosterone and the general activity of female rats exposed to a aperiodic environment].
The effects of bilateral destruction of suprachiasmatic nuclei (SCN) on the temporal patterns of plasma concentrations in ACTH and corticosterone (sequential blood samples from an aortic cannula, at 4 h intervals over 48 h) and of general activity (stabilimeter recordings) were studied in female rats under constant illumination (LL : 10 lx). Under this arrhythmic environment, the SCN lesions induced a syndrome similar to that previously described in a photoperiodic environment (12 L-12 D). This SCN syndrome included : 1) blockade of the ACTH rhythm at baseline levels ; 2) maintained fluctuations of corticosterone, with either circadian or ultradian profiles ; 3) persistent rhythmicity of general activity, with a circadian periodicity in addition to ultradian periods. The persistence of a circadian rhythmicity in the SCN syndrome under arrhythmic environmental conditions, clearly argues in favour of the occurrence of endogenous components of the circadian pacemaker outside the SCN.
Adrenocorticotropic Hormone↗
Neural control of circadian rhythms in plasma ACTH, plasma corticosterone and motor activity.
The circadian rhythms for plasma ACTH and corticosterone (B), as well as motor activity, were explored in female rats after ocular enucleation (O-X), stereotaxic lesion of the suprachiasmatic nuclei (SCN-X) or of midbrain raphe nuclei (R-X), or both O-X and R-X, pharmacological blockade of the serotoninergic (5HT) system by pCPA, sometimes bypassed by 5-HTP, or 5-HT denervation of the SCN by local injection of 5,7-DHT. The three circadian rhythms explored responded quite differently to the treatments. In particular, the ACTH and B rhythms lost their usual close correlations. The amplitude and mean level of ACTH fluctuations were depressed after all treatments, but remained normal or were enhanced for B rhythm. ACTH rhythmicity actually was undetectable after SCN-X, pCPA and, in several rats, combined O-X and R-X, whereas persisting circadian and/or ultradian B and locomotor activity rhythms were always measured. The participation of the suprachiasmatic nuclei, the midbrain raphe nuclei and other possible 5-HT components in a complex circadian pacemaker system is discussed.
Adrenocorticotropic Hormone↗
Serotonin and the regulation of pituitary hormone secretion and of neuroendocrine rhythms.
The importance of 5-HT synaptic transmission for induced or cyclic activation of pituitary secretion now seems widely agreed upon. Raphe structures, the suprachiasmatic nucleus, and, hypothetically, identified mesencephalic 5-HT containing neurons can be assumed to represent parts of the neuronal circuitry of a central clock which synchronizes neuroendocrine rhythms. Cyclic input from the pineal gland may also be involved, though the meaning of this has not yet been clearly established. The primary role of the transmitter may be to modulate transmission to neurosecretory neurons at the output of this clock. This modulation is not hormone-specific and affects, simultaneously, several endocrine functions. 5-HT has also been shown to facilitate the pituitary response to discrete neuroendocrine reflexes, such as the suckling-induced release of prolactin. 5-HT interactions with hormone control provide a good illustration of the neuromodulatory role of the amine.
Animals↗
[Stress responses of the ACTH-corticosterone and LH-testosterone systems in male rats given naloxone].
A single injection of naloxone (1 mg/kg s. c.) increased plasma baseline levels by 6 times for ACTH, 17 times for corticosterone, 3 times for LH and 2 times for testosterone. A concomitant ether-stress induced a further 6 fold increment in ACTH and an additional 2 fold increment in corticosterone, both hormones attaining their similar levels to those after ether-stress alone. On the other hand no further increment was observed for LH and testosterone, which actually were more stimulated by naloxone than by stress alone. The tonic inhibition exerted by endogenous opiates on ACTH and LH appears, therefore, to interfere with stress in a different way for the two neuroendocrine systems considered.
Adrenocorticotropic Hormone↗
[Correlation between the circadian rhythms of plasma ACTH and corticosterone, and of motor activity, evolving freely after ocular enucleation in the rat].
21, 35 and 60 days after bilateral ocular enucleation a similar phase-shift vs an environmental 12 L-12 D photoperiod was observed in the circadian rhythms of plasma ACTH and corticosterone (B) and of motor activity. This phase-shift is indicative of free-running endogenous circadian rhythms whose period was estimated at 2492-24.3 h. The rhythms' amplitude (C) appeared decreased at 21 d for both hormones, and subsequently for ACTH only, whereas the rhythms' mean levels (Co) were reduced for ACTH and augmented for B. The amount of total motor activity per day decreased progressively down to 60% of controls at 60 d. Under otherwise non-fluctuating conditions the photoperiod appears, therefore as a main synchronizer to the endogenous pace-maker(s) driving those hormonal and behavioral rhythms.
Adrenocorticotropic Hormone↗
Serotoninergic system and circadian rhythms of ACTH and corticosterone in rats.
The circadian rhythms of plasma ACTH and corticosterone and of locomotor activity were explored in chronically cannulated female rats, after elimination of serotoninergic (5HT) innervation of the SCN (suprachiasmatic nuclei) either by stereotaxic lesion of the median and dorsal midbrain raphe nuclei (RX) or by local injection of SCN with the neurotoxin 5,7-dihydroxytryptamine (5,7DHT). Completeness of 5HT denervation was checked on serial sections of the hypothalamus either by the Falk-Hillarp technique or by radioautography. Neither lesion eliminated the intrahypothalamic 5HT system, which, however does not take part in the 5HT innervation of the SCN. In both experimental series, the circadian rhythms of the three parameters investigated were maintained in unchanged phase relationships compared to the sham-lesioned controls, and with respect to the photoperiod (12 light-12 dark). However, the estimated amplitudes of the ACTH rhythms dropped by 43% (RX) to 47% (5,7DHT) and their mean levels by 44% (RX) to 60% (5,7DHT), whereas the corticosterone rhythm displayed normal amplitude and its mean level rose by 24% (RX) or 38% (5,7DHT). In regard to locomotor activity rhythm, the most noticeable alteration was a 25-55% increase in the light-phase activity of both experimental groups with a correlative increase in the L/D activity ratio. The essential role of 5HT innervation of the SCN therefore seems to be to facilitate circadian control of the ACTH rhythm.
Adrenocorticotropic Hormone↗
Temporal relationships between the circadian rhythmicity in plasma levels of pituitary hormones and in hypothalamic concentrations of releasing factors.
Ovariectomized female rats were implanted with estradiol containing silastic implants to induce constant circulating levels of the steroid, and sacrificed every 2 h in order to determine neuroendocrine rhythms. Under these conditions, we observed very marked circadian fluctuations in the hypothalamic concentrations of corticotropin-releasing factor (CRF), luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH), and in plasma levels of adrenocorticotropin (ACTH), corticosterone, luteinizing hormone (LH) and prolactin; the amplitude of the prolactin cycle was in particular much higher than in non-chronically estrogenized animals. The daily variation in CRF, ACTH and corticosterone showed significant rank correlations. Changes in hypothalamic content of LHRH and TRH were biphasic; the increase observed during the light period was abruptly interrupted by a depletion episode, coincident with the period of maximal LH and prolactin secretion, respectively. The initial phase of ACTH, LH and prolactin increments occurred between 11.00 and 15.00 h, and was relatively well synchronized. The steepest rise in ACTH and prolactin occurred at the same time, and preceded that of LH by a constant lag of about 2 h. After that initial period, secretion kinetics of the three hormones followed an independent pattern. The data suggest that increased secretion of several hormones results from activation of neural mechanisms occurring within a limited period of the 24-hour cycle.
Adrenalectomy↗
[Effect of the time of administration of 5-hydroxytryptophan on the restoration of circadian stimulation of ACTH secretion in rats treated with p-chlorophenylalanine].
In female rats kept under a photoperiod of 12L-12D (50 lux from 07.00-19.00 h) the pharmacological blockade of serotonin synthesis by pCPA (2 X 300 mg/kg i.p.) obliterated the diel ACTH stimulation, which could, however be restored by an additionnal 5-HTP injection (60 mg/kg i.p.), provided that the serotonin precursor was administered at 11.00 h. If injected at 23.00 h the same dosage of 5-HTP failed to elicit any increase in plasma ACTH. The circadian ACTH rhythm appears, therefore to depend upon a daily activation of the serotoninergic system occurring 4 h after the onset of the light phase.
5-Hydroxytryptophan↗
Effects of lesions of the suprachiasmatic nuclei and of p-chlorophenylalanine on the circadian rhythms of adrenocorticotrophic hormone and corticosterone in the plasma, and on locomotor activity of rats.
Adrenocorticotrophin (ACTH) and corticosterone in the plasma of adult female rats were measured sequentially at 4 h intervals for 24 h before and after lesions of the suprachiasmatic nuclei or treatment with p-chlorophenylalanine (to inhibit serotonin synthesis). After lesions or p-chlorophenylalanine treatment, the concentrations of ACTH were diminished relative to those in control animals and rhythmic changes could not be detected. However, injection of animals, pretreated with p-chlorophenylalanine, with 5-hydroxytryptophan (60 mg/kg) 8 h before the time when plasma ACTH is maximal in intact animals, stimulated ACTH secretion up to control values. Mean corticosterone concentrations in plasma remained unchanged (after lesions) or increased (after p-chlorophenylalanine). This increase was associated with an increased minimal concentration of corticosterone. After both treatments there was evidence of continued circadian or ultradian rhythms of corticosterone concentration. Locomotor activity of female rats given identical treatment, but without blood sampling, indicated that nocturnal activity was diminished after lesions whereas diurnal activity was enhanced after p-chlorophenylalanine treatment. Periodicity analysis detected the persistence of free-running circadian, and sometimes ultradian activity, rhythms. Adrenalectomy did not alter further the activity pattern observed in rats with lesions. These results therefore support the proposition that both the suprachiasmatic nuclei and the serotoninergic system play an irreplaceable role in the mechanism of ACTH secretory rhythms. The suprachiasmatic nuclei are also important for synchronization of locomotor activity and corticosterone rhythms, which may both persist after the suppression of ACTH rhythms.
5-Hydroxytryptophan↗
Temporal relationships between the diurnal rhythm of hypothalamic corticotrophin releasing factor, pituitary corticotrophin and plasma corticosterone in the rat.
Plasma corticosterone (fluorometric assay), pituitary ACTH (bioassay using isolated adrenal cells) and hypothalamic corticotrophin releasing factor (CRF) (bioassay using isolated pituitary cells) were measured singly in groups of six female rats which were killed at 11.00, 15.00, 19.00, 21.00, 23.00, 01.00, 03.00, 05.00, 07.00 and 11.00 h, after 5 weeks of adaptation to a photoperiod of 12 h light: 12 h darkness. Locomotor activity was recorded continuously, using actographic cages, and the waking/sleep pattern was recorded by electroencephalography from chronically implanted control rats during the first hours of the light span. The three hormones msured fluctuated with a 24 h rhythmicity, with extreme values ranging between 4-12+/-1-42 and 31-78+/-194(S.E.M.) microng/100 ml for corticosterone, 4486+/-269 and 16629+/-882 micronu/mg pituitary for ACTH, and 439+/-20 and 1270+/-39 micronu. ACTH production/hypothalamus/10(5) pituitary cells. The onset of the ascending phase of the rhythm started during the first 2 h of light for CRF, 2 h later for ACTH, and again 2 h later for corticosterone. Similarly, the estimated acrophase of the rhythms occurred respectively, 9-4 (CRF), 10-3 (ACTH) and 14-4 h (corticosterone) after onset of light. These phase relationships point to a central origin of the adrenal rhythm. The diurnal activation of CRF at the very beginning of the light phase was concomitant with an almost immediate reduction of the locomotor activity and onset of sleep. These correlations favour the hypothesis of a common temporal control of both the adrenal and the sleep/waking rhythms.
Adrenocorticotropic Hormone↗
Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiologial disorders in rats.
The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1 beta and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1 beta levels and (4) more extensive degradation of the circadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms--but AOR more than OR--caused a blockade of the circadian rhythmicity of major physiological variables, the loss of normal correlations between ACTH and CORT, and inflammatory-immune hyperreactivity. These pathophysiological disorders may all be parts of a complex chronic stress syndrome.
Adrenocorticotropic Hormone↗
Chronic restraint enhances interleukin-1-beta release in the basal state and after an endotoxin challenge, independently of adrenocorticotropin and corticosterone release.
To explore the interactions between the hypothalamic-pituitary-adrenocortical axis and the immune system under stress conditions, we used an experimental rat model for chronic tail-restraint devised earlier for ground studies in space physiology. The system was used in two positions: (1) the orthostatic restraint position (OR) and (2) the antiorthostatic position (AOR) after the rat hind limbs had been raised by a head-down tilt. After 7 days of either restraint, sequential blood samples were taken via an indwelling aortic cannula, before and at various time intervals between 15 and 300 min after an intravascular infusion of 25 micrograms/kg lipopolysaccharide (LPS). The plasma titers of adrenocorticotropin (ACTH), corticosterone (CORT) and interleukin-1 beta (IL-1 beta) were assayed. Under basal conditions, both OR and AOR restraints induced a 5-fold increase in IL-1 beta with no significant changes in ACTH and CORT levels. A robust increase in all three variables was observed after LPS injection. However, the IL-1 beta response to LPS was significantly higher in both restrained groups than in controls. Both the amplitude and the percentage of individually restrained rats displaying elevated IL-1 beta levels were increased up to 5 h. In contrast, the ACTH and CORT post-LPS responses were normal in the OR group. They were unusually dissociated in the AOR rats, which displayed depressed ACTH levels associated with slightly increased CORT levels. Our results suggest that immune-neuroendocrine responses to chronic restraint stress may differ from those generally observed in acute stress.
Adrenocorticotropic Hormone↗