Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently demonstrated that the endozepine octadecaneuropeptide (ODN) exerts an inhibitory influence on corticotropin-releasing hormone (CRH) mRNA expression. The effect is mediated by GABAA receptors and is reversed by adrenalectomy. In order to investigate the involvement of peripheral steroids and more particularly of glucocorticoids in the ODN modulation of CRH mRNA expression, we have evaluated, in adrenalectomized and castrated male rats (ADX/CX), the effect of dexamethasone (DEX) pretreatment on CRH mRNA expression induced by central injection of ODN. Variations in the CRH mRNA expression in the hypothalamic paraventricular nucleus have been studied using quantitative in situ hybridization. The intracerebroventricular injection of ODN (4 microg/kg), as previously reported, induced a significant inhibition of CRH mRNA expression in sham-operated rats (-33%). This inhibition was reversed in ADX/CX male rats (+65% vs. sham vehicle-injected rats and +20% vs. ADX/CX vehicle-injected rats). Pretreatment with DEX (5 mg/kg) during 4 days induced in ADX/CX rats a decrease of 22% (vs. ADX/CX vehicle-injected rats) in the CRH mRNA signal, which became comparable to that observed in sham vehicle-injected rats. Pretreatment of ADX/CX animals with DEX prevented the ODN-induced increase in CRH mRNA expression, inducing rather a 16 and 30% inhibition when compared to vehicle- and ODN-injected ADX/CX rats, respectively. Moreover the CRH mRNA levels observed in ODN-injected ADC/CX rats were higher than those observed in sham vehicle- and sham ODN-injected rats (+16% vs. sham vehicle-injected rats and +63% vs. sham ODN-injected rats). These results indicate that dexamethasone treatment in ADX/CX rats can restore mRNA levels to those observed in sham-operated animals but not the inhibiting effect induced by ODN. Together with previous findings, these results suggest that adrenal and/or gonadal factor(s) other than glucocorticoids are involved in ODN modulation of the HPA axis.
 ...
PMID:Role of glucocorticoids in the modulation of corticotropin-releasing hormone mRNA level by the endogenous benzodiazepine receptor ligand octadecaneuropeptide in rat brain. 970 76

Acute stress stimulates the expression and release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from the hypothalamus, and the pro-opiomelanocortin products beta-endorphin and ACTH from the anterior pituitary. These neuropeptides are also expressed in immune tissues, and it has been proposed that they may modulate immune responses to stress through paracrine mechanisms. We subjected rats to restraint stress or central injection of interleukin (IL)-1beta to determine whether these acute stimuli can alter the expression of neuropeptides in the spleen and thymus. Restraint stress significantly increased the contents of all these neuropeptides in thymic, but not splenic, extracts. A single icv injection of IL-1beta increased contents of CRH, AVP, ACTH and beta-endorphin in the spleens of both sham-operated and adrenalectomised (ADX) rats. IL-1beta increased thymic contents of CRH and ACTH in sham-operated rats but these increases were not observed in ADX rats. These results suggest that the effects of IL-1beta on neuropeptide expression in the spleen are independent of glucocorticoids, whereas IL-1beta stimulation of neuropeptide expression in the thymus is dependent on circulating glucocorticoids. There were significant correlations between increases in CRH, ACTH and beta-endorphin in the spleen, and between CRH and ACTH in the thymus, consistent with the suggestion that IL-1beta-induced increases in ACTH and beta-endorphin may be mediated through CRH. These results provide evidence that stressors can directly influence neuropeptide expression in immune tissues. Thus stress may influence immune functions through paracrine mechanisms involving locally synthesised neuropeptides as well as through activation of the hypothalamo-pituitary-adrenal axis.
 ...
PMID:Effects of Acute Stress or Centrally Injected Interleukin-1beta on Neuropeptide Expression in the Immune System. 978 62

The effect of gama-aminobutyric acid (GABA) on release of adrenocorticotropin (ACTH) from anterior pituitary quarters of male SD rats adrenalectomized for 96 hrs was investigated using the perfusion technique in vitro. Application of bicuculline (10(-6)mol/L), a specific GABA-A antagonist, resulted in a significant release of ACTH from perfused anterior pituitary quarters. But the same concentration of bicuculline had no effect on the release of ACTH from dispersed anterior cells of ADX rats in vitro. Taken together, these results suggest that GABA may play an important inhibitory role on ACTH secretion from pituitary in adrenalectomized rats.
 ...
PMID:[Bicuculline stimulates the release of adrenocorticotropin (ACTH) from rat anterior pituitary quarters]. 1032 69

The present study was designed to determine whether the glucocorticoid inhibitory feedback mechanism plays a role in the well-known tolerance of the neuroendocrine-immune axis response to repeated endotoxemia. Adult male rats underwent adrenalectomy (ADX) and were implanted with a subcutaneous corticosterone (compound B, CB, 75 mg) pellet, or sham operated and implanted with a placebo pellet. On the morning of day 8 after surgery (experimental day, D1), all rats received an intravenous injection of lipopolysaccharide (LPS) (25 microg/kg body weight) which was repeated daily until D5. Blood was drawn via intravenous indwelling catheters before (sample time zero) as well as 1, 2, 3 and 4 h after LPS treatment on D1, 3 and 5 for measurements of corticotropin (ACTH), CB, tumor necrosis factor-alpha (TNF-alpha) and leptin. In sham animals, tolerance to repeated LPS administration was complete by D5 for the corticotrope axis and the immune response. In addition, LPS was found to stimulate leptin secretion on day 1 in intact rats, an effect that also disappeared thereafter. ADX + CB rats showed only a partial tolerance of the corticotrope axis on D5, whereas tolerance of the immune response was similar to that found in sham animals. Interestingly, the acute stimulation of leptin secretion by LPS in ADX + CB rats was qualitatively similar to that of intact controls on D1, but plasma leptin levels were significantly reduced on D3 and 5 compared to controls. Our results demonstrate that the adrenal response tolerance of the hypothalamo-pituitary-adrenal axis to repeated endotoxemia. In addition, our finding that TNF-alpha secretion follows the same pattern in sham-operated and in adrenalectomized animals suggests that unlike the corticotrope axis, tolerance of the immune response does not depend upon stimulated CB levels. The decrease in circulating levels of leptin following ADX is consistent with the stimulatory effects of glucocorticoids on leptin secretion. However, our finding of an acute stimulation of leptin secretion by LPS in ADX + CB animals demonstrates that this effect of endotoxemia is at least partially glucocorticoid independent.
 ...
PMID:Role of glucocorticoids in the response of the hypothalamo-corticotrope, immune and adipose systems to repeated endotoxin administration. 1034 77

The A1 and A2 brainstem noradrenergic cell groups project to the hypothalamic paraventricular nucleus (PVN), which is involved in integrating the stress response. Bi-directional communication between the brain and immune system is well established, with both neuroendocrine and immune responses being activated by lipopolysaccharide (LPS). The mechanisms underlying such activation and differences between alternative routes of administration remain unclear. We examined activation of the PVN and A1/A2 cell groups, by assessing c-fos mRNA, or counting Fos-positive neurons in either the PVN or in brainstem A1/A2 cell groups 3 h after intracerebroventricular (i.c.v.) LPS, in control and adrenalectomized (ADX) rats. We also measured corticotropin-releasing hormone (CRH) mRNA in the PVN, and plasma corticosterone (CORT) levels. A group of ADX/CORT-replaced animals received i.c.v. LPS, and CRH mRNA and Fos peptide in the PVN were analysed. ADX increased CRH mRNA in the PVN, as did LPS, but no enhancement of this response was seen in LPS/ADX animals. C-fos mRNA also increased in both the PVN and the A2 cell group following LPS, but this response was potentiated by ADX. Fos peptide-containing cells increased in the PVN and A2 following LPS, and this change was amplified by ADX. Only 11.25% of Fos was found in DBH-positive (putative noradrenergic) neurons, suggesting activation of neurons containing other transmitters. ADX/LPS/CORT animals showed numbers of Fos neurons in the brainstem, and CRH mRNA levels in the PVN which were comparable to intact/LPS animals. Central LPS activates the hypothalamo-pituitary-adrenal axis, a process mediated partly by brainstem noradrenergic neurons, suggesting the involvement of afferent/efferent pathways within the brain. Peripheral administration of LPS involves activation of vagal inputs leading to the nucleus tractus solitarius. We suggest that centrally administered LPS activates the A2 cell group by a mechanism independent of the vagus. In the absence of CORT, despite the lack of a CRH mRNA response, an exaggerated c-fos and peptide response to LPS is observed, which is reversed following CORT pretreatment.
 ...
PMID:Central LPS-induced c-fos expression in the PVN and the A1/A2 brainstem noradrenergic cell groups is altered by adrenalectomy. 1051 80

Considerable evidence supports a role for brainstem adrenergic and noradrenergic inputs to corticotropin-releasing hormone (CRH) cells of the hypothalamic paraventricular nucleus (PVN), in the control of hypothalamic-pituitary-adrenocortical (HPA) axis function. However, little is known about specific adrenoceptor (ADR) subtypes in CRH-containing cells of the PVN. Here we demonstrate, using dual in situ hybridization, that mRNA encoding alpha(1b) ADR is colocalized with CRH in the rat PVN. Furthermore, we confirm that these alpha(1b) ADR mRNA-containing cells are stress-responsive, by colocalization with c-fos mRNA after restraint, swim, or immune stress. To determine whether expression of alpha(1b) ADR mRNA is influenced by circulating glucocorticoids, male rats underwent bilateral adrenalectomy (ADX) or sham surgery, and were killed after 1, 3, 7, or 14 d. In situ hybridization revealed levels of alpha(1b) ADR mRNA were increased in the PVN 7 and 14 d after ADX, but were not altered in the hippocampus, amygdala, or dorsal raphe. Additional rats underwent ADX or sham surgery and received a corticosterone pellet (10 or 50 mg) or placebo for 7 d. Corticosterone replacement (10 mg) reduced the ADX-induced increase in PVN alpha(1b) ADR mRNA to control levels, whereas 50 mg of corticosterone replacement resulted in a decrease in PVN alpha(1b) ADR mRNA as compared with all other groups. Furthermore, levels of plasma corticosterone were significantly correlated (inverse relationship) with alpha(1b) ADR mRNA in the PVN. We conclude that alpha(1b) ADR mRNA is expressed in CRH-containing, stress-responsive cells of the PVN and is highly sensitive to circulating levels of corticosterone. Because activation of the alpha(1B) adrenoceptor is predominantly excitatory within the brain, we predict that this receptor plays an important role in facilitation of the HPA axis response.
 ...
PMID:Expression of alpha(1b) adrenoceptor mRNA in corticotropin-releasing hormone-containing cells of the rat hypothalamus and its regulation by corticosterone. 1055 17

Corticotrophin releasing factor (CRF) and beta-endorphin (beta EP) containing neurons are shown to be present in the hypothalamus and both neurons are found at the paraventricular nucleus (PVN). Steroid hormones have been found to alter the plasma level of these neurotransmitters. Glycyrrhizic acid (GCA) is the active component of liquorice. GCA inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (11HSD) which is needed for the inactivation of the steroid pathway, so therefore would cause changes to these neurons. The aim of this study was to investigate the effects of GCA as well as deoxycorticosterone (DOC) and dexamethasone (DM) on the modulation of CRF and beta EP containing neuron at the PVN of the hypothalamus. Rats were given either DM, DOC or GCA and adrenalectomized (ADX) and given either DM or DOC. At the end of treatment rats were transfused transcardially before sacrifice and the brain were dissected for immunohistochemical analysis. We found that immunostaining of the CRF containing neurons demonstrate a reduction in the number of positive neurons in DM treated rats. DOC and GCA treated rats showed the same result as in DM rats but the reduction is less. ADX, DM, DOC and GCA treated rats did not show any changes in the number of beta EP containing neurons but naloxone increased the number of beta EP containing neurons markedly. In conclusion, GCA and DOC have similar effects on CRF and beta EP containing neurons at the PVN.
 ...
PMID:Effects of glycyrrhizic acid and steroid treatment on corticotropin releasing factor and beta-endorphin containing neurons of the hypothalamus of the rat. 1087 79

We have used in situ hybridization and radio-immunoassay to compare temporal dynamics of components in the hypothalamo-pituitary limb of the hypothalamo-pituitary-adrenal axis during sustained hypovolemic stress in adrenalectomized (ADX) rats to those previously reported in intact animals. We asked three questions: first, does corticotropin-releasing hormone (CRH) gene transcription occur in neuroendocrine neurones of the hypothalamic paraventricular nucleus (PVH) of ADX rats, and if so, how is it temporally organized; second, what is the expression pattern of the vasopressin and other genes known to be colocalized in these neuroendocrine neurones; third, if adrenocorticotropin hormone (ACTH) secretion occurs, what is its temporal profile? We found that sustained hypovolemia evoked a brief episode of CRH gene transcription in ADX rats that occurred earlier than in intact rats. However, in contrast to saline-injected controls, this activation was not maintained because declines in CRH hnRNA and mRNA were seen as the stress continued. Although increased vasopressin gene transcription was not seen in intact hypovolemic rats, robust increases were measured throughout in ADX rats, suggesting that in the absence of corticosterone the vasopressin gene is transcribed preferentially to the CRH gene during sustained hypovolemia. c-fos and preproenkephalin mRNA profiles also exhibited earlier onsets compared to intact rats. Finally, the onset and duration of ACTH secretion was the same in ADX rats as previously reported in intact rats. Collectively, these data support two hypotheses regarding the actions of corticosterone. First, that it provides some form of facilitatory signal allowing neuroendocrine CRH transcriptional mechanisms to remain active during sustained hypovolemia. Second, that it strongly inhibits the response of the vasopressin gene to hypovolemic stress.
 ...
PMID:Adrenalectomy dramatically modifies the dynamics of neuropeptide and c-fos gene responses to stress in the hypothalamic paraventricular nucleus. 1092 82

The present study was conducted to assess the effect of leptin and corticosterone on the expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC) and agouti-related protein (AGRP) in the mouse brain. To this end, a 3 x 3 factorial experiment was designed in which adrenalectomized (ADX) ob/ob mice were treated with leptin and corticosterone. Leptin and corticosterone downregulated CRH expression in the paraventricular hypothalamic nucleus (PVH). Leptin prevented the stimulating effects of ADX on the expression of CRH and the combination of small doses of leptin and corticosterone was as potent as the high dose of corticosterone in suppressing CRH mRNA expression in the PVH. Leptin and corticosterone enhanced the expression of CRH in the central nucleus of amygdala and in the bed nucleus of the stria terminalis. In addition, the present results confirmed the downregulating effects of leptin on the expression of AGRP mRNA in the hypothalamic arcuate nucleus (ARC), and demonstrated that this effect was more apparent in ADX mice treated with corticosterone than in ADX mice not supplemented with corticosterone. Also, leptin and corticosterone had opposite effects on the expression of POMC in the ARC. The opposite effect of leptin and corticosterone on the expression of POMC and AGRP seems consistent with the reported effects that these hormones and peptides have on food intake and thermogenesis, suggesting that the modulation of POMC and AGRP expression can be a mechanism whereby leptin and corticosterone exert their effects in the regulation of energy balance. In contrast, the similarity in the action of leptin and corticosterone is not a priori consistent with a role of CRH in the effects of these hormones in the regulation of energy balance. The downregulating effect of leptin on the expression of CRH in the PVH strongly suggests that leptin can be a potent regulator of hypothalamic-pituitary-adrenal axis activity. Finally, the present results suggest that the effects of leptin on the expression of CRH, POMC and AGRP are not curbed by glucocorticoids.
 ...
PMID:Effects of leptin and corticosterone on the expression of corticotropin-releasing hormone, agouti-related protein, and proopiomelanocortin in the brain of ob/ob mouse. 1134 Mar 36

We investigated the responses of the hypothalamic-pituitary-adrenal (HPA) axis during experimental colitis induced by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid in the rat. On days 3 and 7 after induction of colitis, the corticotropin-releasing hormone (CRH) mRNA level in the parvocellular paraventricular nucleus (pPVN) of the hypothalamus was reduced, the plasma ACTH level remained at the basal level, and the plasma corticosterone (Cort) level was high. Induction of colitis on day 3 after adrenalectomy with Cort pellet replacement (ADX + Cort) resulted in a marked increase in CRH mRNA on day 7 after induction of colitis compared with noncolitic ADX + Cort animals. Pair feeding to match the food intake of the colitic animals resulted in no significant change in CRH mRNA in the pPVN, plasma ACTH, and Cort compared with healthy control animals. These findings indicated that CRH mRNA expression in the pPVN was inhibited by glucocorticoid feedback during this experimental colitis, and the decrease in food intake during colitis was not simply responsible for the expression of CRH mRNA. It is inferred that the HPA axis including the CRH level in the pPVN is altered in patients with inflammatory bowel disease.
 ...
PMID:HPA-axis responses during experimental colitis in the rat. 1195 75


<< Previous 1 2 3 4 5 6 7 8 9 Next >>