Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The febrile and neuroendocrine responses to circulating endotoxin are effected, at least in part, by a central action of prostaglandins with interleukins serving as intermediaries. Data from rodents suggest that prostaglandin and interleukin (IL-1 beta) synthesis in response to endotoxin challenge may occur within the circumventricular organs of the brain, especially the choroid plexus; the present study investigated this possibility using the sheep as an experimental model. A pyretic dose of bacterial endotoxin (40 micrograms lipopolysaccharide) was given intravenously to sheep (n = 5) and the effect on gene expression in the choroid plexus after a 40 min interval was compared with that observed in vehicle-treated animals (n = 5) using in situ hybridisation histochemistry. Evidence of activational and synthetic events following endotoxin administration was provided by significant increases in c-fos (P < 0.05) and IL-1 beta (P < 0.01) mRNA expression. Constitutive cyclooxygenase (cox-1 mRNA) and inducible cyclooxygenase (cox-2 mRNA) synthesis were unchanged. The investigation also sought to provide evidence for endotoxin effects on neuroendocrine activity in this species by examining changes in hypothalamic gene expression. The results showed that c-fos mRNA increased in the paraventricular (P < 0.01) and supraoptic (P < 0.05) nuclei and that CRH mRNA was upregulated in the paraventricular nucleus (P < 0.001). However, in agreement with previous work, there was no change in vasopressin gene expression although oxytocin mRNA was enhanced throughout the paraventricular nucleus (P < 0.05). These findings suggest the following: (1) possible involvement of the choroid plexus in the response of sheep to immunological challenge: (2) endotoxin-induced changes in gene expression in the ovine hypothalamus similar in those caused by other stressors: and (3) possible changes in oxytocin synthesis concomitant with fever in the sheep.
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PMID:Bacterial endotoxin-induced gene expression in the choroid plexus and paraventricular and supraoptic hypothalamic nuclei of the sheep. 903 17

The effects of cytokines in stimulating neurohypophysial hormone release have not been well characterized. In the present study, we have investigated the effect of intraperitoneal injection of recombinant human interleukin (IL)-1 beta on oxytocin release in sham-operated controls, adrenalectomized (ADX) rats and ADX rats given either low or high doses of the synthesis glucocorticoid dexamethasone. In a second study, we determined the effect of central injection of IL-1 beta on both oxytocin and arginine vasopressin (AVP) release in sham-operated and ADX rats. We were unable to demonstrate an increase in plasma oxytocin in intact rats in response to intraperitoneal injection of IL-1 beta. In contrast, we found a substantial and sustained increase in plasma oxytocin concentrations in ADX rats. This stimulation was abolished by treatment with dexamethasone at both the low and high doses. Following central injection of IL-1 beta, we were unable to demonstrate any increase in either oxytocin or AVP, despite the ability of this dose of cytokine to stimulate the hypothalamo-pituitary-adrenal axis, as evidenced by increased circulating corticosterone. It appears that circulating glucocorticoids may exert a tonic inhibitory effect on the release of oxytocin in response to peripheral stimulation by IL-1 beta.
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PMID:Interleukin-1 beta-induced effects on plasma oxytocin and arginine vasopressin: role of adrenal steroids and route of administration. 926 47

It has been well documented that the medial parvocellular subnucleus of the hypothalamic paraventricular nucleus (PVN) participates in immune regulation by releasing corticotrophin-releasing hormone (CRH), which triggers the hypothalamus-pituitary-adrenal axis, leading to immunosuppression. Little is known about other possible influences of PVN on immunomodulation. Evidence, however, has been accumulating recently, indicating possible involvement of other subnuclei of this nucleus. By using the c-fos technique, the present study investigated the neuronal groups of the PVN that were activated in response to intracerebroventricularly administered IL-1 beta. In addition to strong Fos expression in the dorsal part of medial parvocellular subnucleus of the PVN, where CRH neurons are located, two more neuronal groups were found to express Fos protein. One of which was the oxytocin-immunoreactive magnocellular neurons, mainly concentrated in the anterior and medial magnocellular subnuclei of the PVN. The magnocellular PVN subnuclei are known to project to, and release their hormones, in the posterior pituitary. Another group of Fos-immunoreactive neurons were found in the brainstem and spinal cord projecting area of the PVN. By combining retrograde tracing technique and Fos immunohistochemistry, it was proved that many of the spinal cord projecting PVN neurons were activated following IL-1 beta administration, through which the spinal cord sympathetic outflow might be regulated. The present study indicates that the hypothalamic PVN may serve as an integrative center for immunomodulation via three channels, i.e., the CRH and oxytocin neuroendocrinological and the PVN-spinal cord sympathetic neural channels.
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PMID:Evidence for hypothalamic paraventricular nucleus as an integrative center of neuroimmunomodulation. 950 Jan 46

Systemic administration of the cytokine IL-1 beta produces a significant release of ACTH into the plasma and activation of hypothalamic oxytocin (OT) and corticotropin releasing factor (CRF) cells. However, the mechanism(s) by which systemic IL-1 beta induces these responses is not clear. In the present study, we have investigated the proposal that catecholamine cells of the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS) can relay circulating IL-1 signals via a prostaglandin-dependent mechanism to effect the HPA axis responses in the rat. Intra-arterial administration of IL-1 beta (1 pg/kg) to otherwise untreated animals produced a prominent release of ACTH into the plasma, substantial c-fos expression in paraventricular medial parvocellular (mPVN) corticotropin releasing factor (CRF) cells, supraoptic (SON) and paraventricular nucleus (PVN) OT cells, area postrema cells, NTS and VLM catecholamine cells and cells of the central amygdala. Pretreatment with the prostaglandin synthesis inhibitor, indomethacin (10 mg/kg body weight ia) 15 min before IL-1 beta administration (1 pg/kg ia) significantly reduced plasma ACTH release and c-fos expression in PVN and SON OT cells and MPVN CRF cells, in addition, the area postrema, A1 and C1 catecholamine cell groups of the VLM and A2 and C2 catecholamine cell groups of the NTS, all exhibited concomitant reductions in c-fos expression. Conversely indomethacin administration did not alter the IL1 beta-induced expression of c-fos in the central amygdala. These data suggest that central pathways involved in the IL-1 beta-induced activation of the HPA axis and OT cells are, at least in part, dependent upon prostaglandin synthesis. It is proposed that neurons in the area postrema, NTS and VLM might mediate this IL-1 beta-induced activation of hypothalamic CRF and OT cells and release of ACTH into the plasma.
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PMID:Indomethacin attenuates oxytocin and hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1 beta. 970 Jun 79

Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1-beta and tumor necrosis factor-alpha, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-alpha, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.
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PMID:Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances. 1860 75


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