摘要:

An ultradian rhythm in adrenal secretion of corticosterone has been described in awake rats using intra-adrenal microdialysis. To determine the role of the autonomic innervation of the adrenal on the expression of the corticosterone rhythm, adrenal extracellular fluid was sampled by intra-adrenal microdialysis in intact (CTRL) and splanchnicectomized (SPLNX) rats 5-7 h before (light period) and after dark onset (dark period). Experiments conducted 1, 2, or 5 days after surgical insertion of the microdialysis probe consisted of continuous collection of dialysate at intervals of 10 min. Time domain pulse detection using PC-PULSAR showed that 5 days after surgery, SPLNX decreased interpulse interval (IPI) during the light period, but had no effect during the dark period, resulting in the loss of the diurnal rhythm in corticosterone secretion. Although diurnal modulation of both pulse amplitude and pulse frequency was observed, only the frequency was altered by SPLNX. In CTRL animals IPI increased at 5 days postsurgery, relative to 1 and 2 days, but the amplitude of normalized secretory pulses did not change. The decrease in IPI caused by SPLNX was observed 5 days, but not 1 or 2 days after surgery, suggesting that surgical stress obscures the inhibitory effect of splanchnic neural activity. Power spectral analysis showed significant periodicities in corticosterone secretion rate in individual CTRL and SPLNX animals at 1, 2, and 5 days. One day after surgery, SPLNX reduced the frequency of the ultradian rhythm detected by power spectral analysis. This finding suggests that splanchnic neural activity may increase pulse frequency in stressed rats, in opposition to the effect seen after extended recovery from surgery. In conclusion, our data suggest that the nadir of the diurnal rhythm in corticosterone secretion results in part from neural inhibitory control. Splanchnic neural innervation may also have an excitatory role in the adrenocortical stress response.

ISSN:0028-3835    

DOI:10.1159/000126645

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Anandamide (arachidonylethanolamide), an endogenous ligand of the cannabinoid receptor, was recently isolated from porcine brain. We report here for the first time on the effect of this ligand on the hypothalamopituitary adrenal (HPA) axis in comparison to that of the plant cannabinoid Δ9-tetrahydrocannabinol (THC). Intracerebroventricular injection of anandamide or THC (50 or 150 µg/rat) increased significantly the serum levels of ACTH and corticosterone in a dose-dependent manner and caused a pronounced depletion of CRF-41 in the median eminence. These data suggest that anandamide parallels THC in activating the HPA axis via mediation of a central mechanism which involves the secretion of CRF-4

ISSN:0028-3835    

DOI:10.1159/000126646

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The occurrence, cellular distribution and nature of the 27-amino acid form of pituitary adenylate cyclase-activating peptide (PACAP-27) in the adrenal glands of mammals was investigated by means of immunohistochemistry, radioimmunoassay and chromatography. The concentrations (pmol/g wet weight) of PACAP-27-like immunoreactivity (LI) varied considerably between the species examined: mouse (n = 8), 12.1 ± 2.0; hamster (n = 4), 9.1 ± 1.5; rat (n = 13), 2.0 ± 0.3; cow (n = 3), 0.8 ± 0.1, and pig (n = 5), 0.7 ± 0.1. Upon HPLC, the immunoreactivity in extracts of rat, mouse and hamster adrenals coeluted with synthetic PACAP-27 while the immunoreactivity in extracts of cow and pig adrenals eluted as less hydrophobic material. Immunohistochemistry revealed the presence of PACAP-27-LI in the noradrenaline-storing chromaffin cells of the adrenal medulla. No nerve fibers exhibiting PACAP-27-LI could be detected. The effects of drug administration in vivo on the stores of PACAP-27-LI in the rat adrenal were studied and compared with the effects on the adrenal stores of neuropeptide Y (NPY)-LI. Splanchnic activation following insulin-induced hypoglycemia elicited a 41% depletion of NPY-LI 2 h after insulin injection, while the concentrations of PACAP-27-LI remained unchanged. Two days after reserpine administration the stores of PACAP-27-LI and NPY-LI were depleted by 62 and 41%, respectively. Two days later, the concentrations of NPY-LI were increased to 216% of controls, while the concentrations of PACAP-27-LI were similar to that of controls. Taken together with data from the literature, our findings suggest that PACAP may be involved in the regulation of adrenomedullary activity in more than one mammalian species. The stimuli that regulate the synthesis and release of PACAP-27 in the adrenal gland remains to be identified but seems to differ from those involved in the regulation of

ISSN:0028-3835    

DOI:10.1159/000126647

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Interleukin-1 (IL-1) and glucocorticoid hormones represent two key mediators involved in the modulation of the neuroimmunoendocrine response to stress. IL-1 is a potent activator of the hypothalamic-pituitary-adrenal (HP A) axis in rodents. In the immune system, glucocorticoids modulate IL-1 production and a number of IL-1 receptors. However, little information is currently available about the modulatory effects that glucocorticoids might exert on IL-1 receptors in the central nervous system. To this purpose, we carried out a series of studies to investigate the effects of various manipulations of the HPA axis on IL-1 binding to the murine hippocampus. Our results show that IL-1 receptor levels in the hippocampus were slightly decreased below control values in dexamethasone (DEX)-treated animals (0.25 or 1 mg/kg i.p. every 12 h) either in subchronic (5 doses) or chronic (8 days) treatments. Corticosterone (CORT) resulted in a small reduction in IL-1 receptors only when injected subchronically at the dose of 5 mg/kg. When it was given at a lower dose (1.25 mg/kg), injected chronically or implanted subcutaneously as CORT pellets for 8 days, no effect was observed. Neither glucocorticoid modified IL-1 binding when administered as a single injection. Saturation studies after subchronic corticosteroid treatment did not reveal modifications in the number and/or affinity of IL-1 receptors in the hippocampus. The regulation of IL-1 receptors by glucocorticoids was also studied following stimulation of IL-1 production by lipopolysaccharide (LPS). LPS administration (30 µg i.p. 24 and 12 h before sacrifice) resulted in a significant reduction in IL-1 binding, but this effect was not modified by DEX treatment. Exposure to stress (sound, cold exposure or foot shock) once a day for 5 days did not modify IL-1-binding levels in the hippocampus. Moreover, hippocampal IL-1 receptor binding was not changed 2 or 7 days after adrenalectomy. The results of the present study suggest that, in contrast to what has been observed in the immune system, IL-1 receptor levels in the murine hippocampus are relatively resistant to modulation by varying levels of circulating glucocorticoids

ISSN:0028-3835    

DOI:10.1159/000126648

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Nonthyroidal illness is characterized by low thyroid hormone levels and inappropriately normal or decreased TSH levels. To determine whether the hypothalamus contributes to these responses, TRH gene expression in hypophysiotropic neurons of the paraventricular nucleus (PVN) was investigated using semiquantitative in situ hybridization histochemistry in an animal model of nonthyroidal illness. Following the systemic administration of bacterial lipopolysaccharide (LPS; 250 µg/100 g BW), plasma T4, T3 and TSH were reduced but this was not associated with an increase in the content of proTRH mRNA in the PVN as occurs when plasma T4 and T3 concentrations fall during primary hypothyroidism. Constant infusion of human interleukin-1β (IL-1β) into the cerebrospinal fluid also reduced plasma T4 concentration. This persisted for the duration of the infusion but TSH was only suppressed after 7 days of infusion when body weight had declined. By 24 h, the content of proTRH mRNA in the PVN in IL-1β infused animals was significantly reduced from control values. These studies indicate that the peripheral administration of endotoxin or central administration of IL-1β in the rat is associated with a proTRH mRNA content in the PVN that may be inappropriately normal or reduced for the level of circulating thyroid hormone. We propose that the inability of hypophysiotropic neurons to induce TRH gene expression in nonthyroidal illness, when circulating thyroid hormone levels are low, is one of several factors that contributes to the inability of the anterior pituitary to increase its secretion of

ISSN:0028-3835    

DOI:10.1159/000126649

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The neuropeptide α-melanocyte-stimulating hormone (α-MSH) has potent antipyretic and antiinflammatory properties. When administered systemically, the naturally occurring molecule and its COOH-terminal tripeptide sequence inhibit inflammation induced by peripherally applied irritants and intradermal injections of mediators of inflammation such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα). We recently found that α-MSH can act solely within the brain to inhibit inflammation caused by a general irritant applied to the skin. This activity appears to be shared with salicylate drugs and the combined observations suggest the existence of descending neurogenic antiinflammatory signals capable of modulating inflammation in peripheral tissues. To improve our knowledge of the scope of this action of the peptide, α-MSH was injected into the cerebral ventricles (i.c.v.) of mice that had received intradermal injections in the ear of mediators of inflammation: IL-1β, IL-8, leukotriene B4, and platelet-activating factor. The centrally administered peptide inhibited the actions of all of these proinflammatory agents as determined from comparisons with measures of ear edema over time in control animals; this indicates that the central peptide can alter inflammation induced in the periphery by major mediators of inflammation. In tests confined to IL-1β, central administration of α-MSH(11–13) was also effective. These findings support the concept of a descending neurogenic antiinflammatory influence promoted by an action of α-MSH within the brain, an inhibitory influence that is not restricted to modulation of just one or a limited set of the mediators of i

ISSN:0028-3835    

DOI:10.1159/000126650

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

We investigated the lymphocyte interleukin-2 (IL-2) system, which is critically involved in lymphocyte activation, in patients with disorders or the hypothalamic-pituitary-adrenal (HPA) axis. Patients with Cushing’s syndrome (n = 9) showed a significant (p < 0.05) inhibition of phytohemagglutinin (PHA)-stimulated IL-2 secretion by peripheral lymphocytes and a decrease of sensitivity to cortisol inhibition in vitro compared to normal subjects (n = 9). Circulating soluble interleukin-2 receptor (sIL-2R) levels were significantly decreased (p < 0.05), whereas no significant difference was observed in PHA-induced sIL-2R release in vitro. In patients with hypocortisolism (n = 12), in vitro IL-2 synthesis was increased compared to normal subjects and to patients with Cushing’s syndrome (p < 0.01). In vitro sIL-2R release was significantly higher (p < 0.01) compared to patients with Cushing’s syndrome. In contrast to patients with secondary adrenal insufficiency (n = 7), patients with an adrenal origin of hypocortisolism (Addison’s disease, bilateral adrenalectomy; n = 5) showed significantly elevated circulating sIL-2R levels compared to normal subjects and patients with Cushing’s syndrome (p < 0.005). There was no significant difference between the study groups in mitogen-induced DNA synthesis. This is the first description of alterations of cytokine secretion in patients with HPA axis disorders. The contrary effects of long-term hypercortisolism and insufficient or absent adrenal glucocorticoid secretion on IL-2-mediated lymphocyte activation could account for the immune states previously observed in these

ISSN:0028-3835    

DOI:10.1159/000126651

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The present study revealed that the pineal gland expressed basic fibroblast growth factor (bFGF) and FGF-receptor 1 (FGFRl/flg), suggesting that bFGF in the pineal gland acts in an autocrine or paracrine manner, which is mediated by FGFRl/flg. The present study also examined gene expression of the extracellular signal-regulated kinase (ERK) family (ERK 1–3) which may be intracellular signal mediators of growth factors. ERK1 [mitogen-activated protein kinase (MAP-kinase)] was strongly expressed throughout the pineal gland, while expression of ERK2 and ERK3 was not found. These findings suggest the presence of a signal pathway from bFGF to ERK1 via FGFRl/flg in the pineal glan

ISSN:0028-3835    

DOI:10.1159/000126652

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The effect of guanine nucleotides on the binding of 2-[125I]iodomelatonin in membrane preparations of guinea pig spleen was studied. The GTP analogues guanosine 5’-0-(3-thiophosphate) and 5’-guanylimidodiphosphate dose-dependently inhibited the binding. Saturation studies revealed that the presence of GTP analogues either increased the equilibrium dissociation constant (Kd) alone or both increased the Kd and decreased the binding site density (Bmax). Our results suggest that melatonin receptors in the guinea pig spleen, similar to those in the neural and retinal tissues, are coupled to a G protein. This study showed that Na+ and Li+ dose-dependently inhibited 2-[125I]iodomelatonin binding while Mg2+ potentiated the binding. K+ and choline were without significant effects. Low Ca2+ concentrations (1–5 mmol/l) potentiated the radioli-gand binding while higher concentrations were inhibitory. Saturation studies demonstrated that 125 mmol/l Na+ decreased the Bmax while 2.4 mmol/l Ca2+ increased the Bmax and 40 mmol/l Ca2+ increased the Kd. Our results suggest that physiological concentrations of Na+ and Ca2+ may play an important modulatory role on melatonin binding to its receptors in the s

ISSN:0028-3835    

DOI:10.1159/000126653

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Effects of pinealectomy and melatonin replacement on the timing of the preovulatory luteinizing hormone (LH) surge were examined in female rats housed under a light-dark cycle (lights on 06:30–18:30 h). Animals were pinealectomized or sham-operated 21-28 days before bleeding. They were sequentially bled in the afternoon of proestrus through the indwelling cardiac cannula without anesthesia. Proestrous LH surges were observed in all pinealectomized rats, but the onset times of the LH surge in these animals showed a significantly greater variance than those in sham-operated controls. A single melatonin injection at 18:00 or 21:00, shortly before or after the light-dark transition, on the day before proestrus (diestrus II) reduced the variance in the LH surge onset in pinealectomized rats in a dose-dependent manner. In contrast, melatonin injected at 14:00 or 23:00 on diestrus II or at 04:00 on proestrus was ineffective. These results showed that the pineal gland is involved in controlling the timing of the proestrous LH surge in the rat. The pineal signal may be transmitted by melatonin, a major product of the glan

ISSN:0028-3835    

DOI:10.1159/000126654

出版商:S. Karger AG    

年代:1994

数据来源: Karger