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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activation of the magnocellular oxytocin system by different physiological stimuli will require specific genomic responses that may or may not reflect the electrical and short-term secretory activity of the neurones. One of the main determinants of synthetic activity is the rate of transcription and this can be altered acutely by the action of inducible transcription factors (iTFs). Having shown that the expression of two iTFs, the protein products of the c-fos and c-jun genes, does not correlate directly to the electrical activity of magnocellular neurones (Luckman et al., 1994) the expression of leucine zipper iTF mRNAs was measured following different stimuli using combined radioactive and non-radioactive in situ hybridization. Stimuli that are dependent on brainstem afferents such as parturition and systemic injection of cholecystokinin caused co-induction of c-fos and c-jun in oxytocin neurones. Mild osmotic stimulation, a stimulus dependent on forebrain afferents, induced c-fos, fos B and jun B, but inhibited c-jun. Similar patterns of leucine zipper iTF expression have been noted in cultured cells following activation of protein kinases C and A, respectively. Input from the brainstem appears to be mediated, at least in part, by noradrenaline acting on alpha(1)-adrenoceptors. While the forebrain inputs are not well characterised they do appear to include a glutaminergic component that may activate a variety of receptors. Interestingly, another member of the leucine zipper family known to be induced by protein kinase A, inducible cAMP early repressor (ICER), that was previously thought to be restricted to the pineal gland, was expressed in magnocellular neurones following osmotic stimulation but not parturition. Furthermore, the differential expression of iTFs is not limited to this family. Osmotic stimulation influences c-fos, but it also causes the expression of NGFI-A and NGFI-B, members of the zinc finger family of iTFs. By contrast, an acute suckling stimulus is able to induce c-fos and NGFI-A, but not nGFI-B.
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PMID:Stimulus-specific expression of inducible transcription factors in identified oxytocin neurones. 871 50

Plasma oxytocin (OT) levels are strongly correlated with inhibition of ingestion in many models of stimulated food and NaCl intake in rats, but peripheral administration of OT or OT antagonists has little or no effect on these behaviors. These findings led us to propose that central OT secretion from parvocellular neurons occurring in parallel with pituitary secretion from magnocellular neurons acts to inhibit ingestion of both food and salt. Multiple lines of evidence now support this hypothesis: 1) intracerebroventricular (icv) OT administration inhibits food intake in fasted rats and NaCl intake in hypovolemic rats; 2) icv administration of OT-receptor antagonists significantly blunts the effects of anorexigenic agents on food intake and the action of naloxone to inhibit hypovolemia-induced intake of NaCl, but not water; 3) most treatments that inhibit food and/or NaCl intake stimulate expression of c-fos in parvocellular as well as magnocellular OT neurons, indicating simultaneous activation of both centrally-projecting and pituitary-projecting OT neurons; 4) icv treatment with cytotoxic conjugates of ricin A and OT to disable cells bearing OT receptors leads to a disinhibition of NaCl intake similar to that produced by OT antagonists; 5) administration of ethanol, a well known inhibitor of OT secretion, produces effects on stimulated food and NaCl intake in rats analogous to those produced by OT-antagonists and ricin-OT conjugates. In conjunction with studies demonstrating natriuretic effects of circulating OT, these results therefore support the concept of coordinated central and peripheral OT secretion as a mechanism for regulating body solute homeostasis in rats. These phenomena will be used as a framework to discuss and critically evaluate the criteria that are both necessary and sufficient to firmly establish behavioral and physiological functions of centrally-secreted peptides such as OT.
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PMID:Establishing behavioral and physiological functions of central oxytocin: insights from studies of oxytocin and ingestive behaviors. 871 70

In situ hybridization was used to measure the expression of members of the Fos/Jun family of immediate-early genes in hypothalamic neurons in vivo following defined stimuli that utilize different afferent pathways. Only c-jun messenger RNA was expressed in the hypothalamic supraoptic and paraventricular nuclei of control animals. Intravenous infusions of sodium chloride solutions of different tonicity produced a range of plasma osmolalities within physiological limits. While the induction of c-fos and jun B messenger RNAs followed the stimulus intensity, the expression of c-jun was repressed at low levels of stimulation. A higher level of osmotic stimulation was able to co-induce c-jun with the c-fos, jun B and fos B genes, suggesting that other signalling pathways may then be activated. Parturition or systemic administration of cholecystokinin, that activate supraoptic and paraventricular neurons via ascending afferent pathways from the brainstem, both induced c-fos, but not the other genes, in the magnocellular nuclei. Use of double in situ hybridization confirmed that, unlike with osmotic stimulation, induction of c-fos only occurred in oxytocin neurons. These two stimuli did not cause a concomitant repression of c-jun messenger RNA expression in magnocellular oxytocin neurons. These patterns of induction provide evidence for the differential regulation of members of this family of genes in a physiological context.
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PMID:Induction of members of the Fos/Jun family of immediate-early genes in identified hypothalamic neurons: in vivo evidence for differential regulation. 878 63

The present study investigated the effect of central administration of the prostaglandin of E2 type (PGE2) on the distribution of the immediate early gene (IEG) c-fos mRNA and the transcriptional activity of corticotropin-releasing factor (CRF) and its type 1 receptor in the brain of conscious rats. Adult male rats were sacrificed 30 min and 2 h after a single infusion of PGE2 into the right lateral ventricle (2 micrograms/10 microliters) and their brains cut from the olfactory bulb to the end of the medulla in 30 micrometer coronal sections. mRNAs encoding the IEG c-fos and CRF1 receptor were assayed by in situ hybridization histochemistry using 35S-labeled exonic riboprobes whereas the primary transcript (heteronuclear (hn)RNA) for CRF was detected using intronic probe technology as an index of CRF transcriptional activity. Colocalization of c-fos mRNA within CRF, vasopressin (AVP), and oxytocin (OT) neurons was determined by means of a combination of immunocytochemistry and in situ hybridization techniques on the same brain sections. Thirty min after PGE2 injection, a moderate to strong positive signal for c-fos mRNA was detected in multiple structures of the brain such as the medial preoptic area/organum vasculosum of the lamina terminalis, supraoptic nucleus (SON), parvocellular and magnocellular divisions of the paraventricular nucleus (PVN) of the hypothalamus, central nucleus of the amygdala, nucleus of the solitary tract, dorsal motor nucleus of the vagus, area postrema, dorsal division of the ambiguus nucleus, and throughout the choroid plexus and leptomeninges. A smaller but significant c-fos expression was observed in various structures including the subfornical organ, bed nucleus of the stria terminalis, arcuate nucleus, and periventricular nucleus of the hypothalamus. Two h after treatment with the PG, the signal for c-fos mRNA in most of these brain nuclei vanished. In the parvocellular nucleus of the PVN, c-fos was expressed in CRF-immunoreactive (ir) and OT-ir neurons, whereas in the magnocellular part of that nucleus and in the SON, this transcript was essentially colocalized in OT-ir neurons. Activation of CRF neuroendocrine cells was also associated with an increase in CRF transcription as revealed by the selective presence of CRF primary transcript (hnRNA), which was stimulated only in the PVN but not in any other nuclei in the brains of PGE2-treated rats. Central administration of PGE2 also induced expression of the CRF type 1 receptor in the parvocellular PVN. Taken together, these results provide clear anatomical evidence that central PGE2 injection causes specific and selective expression of c-fos in several brain structures recognized to be activated in the brains of endotoxin-challenged rats. It is therefore possible that PG of E2 type plays a crucial role within the CNS in the interface between the immune and nervous systems to modulate neuroendocrine responses, such as the hypothalamic-pituitary-adrenal axis.
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PMID:C-fos mRNA pattern and corticotropin-releasing factor neuronal activity throughout the brain of rats injected centrally with a prostaglandin of E2 type. 889 25

Systemic administration of cholecystokinin (CCK) stimulates neurosecretory oxytocin (OT) and tuberoinfundibular corticotrophin releasing factor (CRF) cells of the hypothalamus. Data from previous studies suggest that A2 noradrengeric neurons of the dorsomedial medulla contribute to the OT cell response, but the role of other medullary catecholamine cells remains unclear. Using c-fos expression as a marker for cellular activity, we have found that CCK (100 micrograms/kg, i.p.) activates substantial populations of tyrosine hydroxylase and phenyl-N-methyl-transferase immunoreactive cells in the medulla, consistent with recruitment of overlapped noradrenergic and adrenergic cell populations in both the ventrolateral and dorsomedial medulla. In the ventrolateral medulla there was a particularly prominent activation of C1 adrenergic neurons at the level of the obex. To directly test the contribution of VLM catecholamine cells to hypothalamic neuroendocrine cell responses to CCK, animals were prepared with unilateral VLM lesions corresponding to those areas that had displayed the most marked response to CCK. VLM lesioned animals treated with CCK displayed a significant although small reduction in paraventricular nucleus (PVN) OT cell c-fos expression ipsilateral to the lesion, but no change in the responses of supraoptic nucleus OT cells or in cells of the medial parvocellular PVN, many of which are CRF cells. These findings indicate that VLM catecholamine cells make little contribution to hypothalamic neuroendocrine cell responses to CCK and thus serve to further highlight the role of dorsomedial catecholamine cells. However, it is now apparent that, in addition to A2 noradrenergic cells, CCK treatment also recruits C2 adrenergic cells of the dorsomedial medulla, many of which have previously been shown to project to the PVN.
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PMID:Involvement of medullary catecholamine cells in neuroendocrine responses to systemic cholecystokinin. 893 58

We investigated whether hypertonicity acts directly on supraoptic neurones to activate c-fos expression. Hypertonic artificial cerebrospinal fluid was infused into the supraoptic nucleus (SON) via a microdialysis probe implanted 24 h previously. The rats were decapitated after 90 min for immunohistochemistry with a Fos protein antibody. Direct hypertonic stimulation increased Fos protein expression in glial cells, identified by glial fibrillary acidic protein immunoreactivity, but not in magnocellular neurones. Similarly, with in situ hybridisation c-fos mRNA expression was predominantly seen in glial cells. Fos expression in SON neurones was stimulated by systemic hypertonicity even with a microdialysis probe in the SON, and magnocellular neurones expressed Fos after direct microinjection of cholecystokinin-8S into the SON. Thus, while direct hypertonic stimulation of SON neurones activates secretion of vasopressin and oxytocin, the c-fos gene is not activated, unlike following systemic hypertonic stimulation. This indicates that excitation of neuronal electrical and secretory activity does not necessarily lead to activation of the c-fos gene. Activation of c-fos expression in glial cells by direct hypertonic stimulation may reflect their role in regulating brain extracellular fluid composition.
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PMID:Direct hypertonic stimulation of the rat supraoptic nucleus increases c-fos expressionin glial cells rather than magnocellular neurones. 901 4

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 present study was designed to delineate the neuronal site, the nature, and the gastrointestinal origin of the stimulation of the hypothalamic magnocellular system induced by the ingestion of sweetened condensed milk. Concomitant localization of the c-fos protein (Fos) with either arginine-vasopressin (AVP) mRNA or oxytocin (OT) mRNA in the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON) revealed that the hypothalamic neurons containing AVP and OT were activated following ingestion of sweetened condensed milk. Expression of c-fos mRNA was also determined in rats implanted with a gastric cannula that allowed for real, sham, and gastric feeding of sweetened condensed milk. The results provide evidence that the stimulation of the PVH and SON induced by sweetened condensed milk originate from oropharyngeal stimuli. Indeed, in real-and sham-fed rats, the postprandial levels of c-fos mRNA in the PVH and SON were significantly higher than the preprandial values, whereas there was no early postprandial rise in c-fos mRNA levels within the magnocellular division of the PVH and SON after gastric feeding. The results of this study also suggested that the stimulation of the PVH and SON induced by sweetened condensed milk was related to the hypertonicity of the milk, indeed, ingestion of an hypertonic solution of sucrose with a carbohydrate content close to that of sweetened condensed milk led to a stimulation of the PVH and SON that was comparable to that induced by the milk, whereas ingestion of an isotonic solution of sucrose did not trigger any significant activation of the PVH and SON. Taken together, the present results indicate that magnocellular neurosecretory neurons are sensitive to oropharyngeal stimuli and further support the view of the existence of oropharyngeal osmoreceptors.
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PMID:Neuronal activation of the hypothalamic magnocellular system in response to oropharyngeal stimuli in the rat. 918 86

Within the central nervous system, glucagon-like peptide-1-(7-36) amide (GLP-1) acts as a transmitter, inhibiting feeding and drinking behavior. Hypothalamic neuroendocrine neurons are centrally involved in the regulatory mechanisms controlling these behaviors, and high densities of GLP-1 binding sites are present in the rat hypothalamus. In the present study we have, over a period of 4 h, followed the effect of centrally injected GLP-1 on plasma levels of the neurohypophysial hormones vasopressin and oxytocin. Plasma levels of corticosterone and glucose were also followed across time after central administration of GLP-1. In conscious, freely moving, and unstressed rats, central injection of GLP-1 significantly elevated plasma levels of vasopressin 15 and 30 min after administration (basal, 0.8 +/- 0.2 pg/ml; 15 min, 7.5 +/- 2.0 pg/ml; 30 min, 5.6 +/- 1.1 pg/ml; mean +/- SEM) and elevated corticosterone 15 min after administration (52 +/- 13 vs. 447 +/- 108 ng/ml, basal vs. 15 min; mean +/- SEM). In contrast, plasma oxytocin levels were unaffected by intracerebroventricular (icv) injections of GLP-1 over a period of 4 h after the injection. The animals given a central injection of GLP-1 developed transient hypoglycemia 20 min after the injection, which was fully restored to normal levels at 30 min. Furthermore, we used c-fos immunocytochemistry as an index of stimulated neuronal activity. The distribution and quantity of GLP-1-induced c-fos immunoreactivity were evaluated in a number of hypothalamic neuroendocrine areas, including the magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) nuclei and the parvicellular neurons of the medial parvicellular subregion of the PVN. The number of c-fos-expressing nuclei in those areas was assessed 30, 60, and 90 min after icv administration of GLP-1. Intracerebroventricular injection of GLP-1 induced c-fos expression in the medial parvicellular subregion of the PVN as well as in magnocellular neurons of the PVN and SON. A slight induction of c-fos expression was seen in the arcuate nucleus and the nucleus of the solitary tract, including the area postrema. In contrast, the subfornical organ, which is a rostrally situated circumventricular organ, was free of c-fos-positive cells after central administration of GLP-1. When the GLP-1 antagonist exendin-(9-39) was given before the GLP-1, c-fos expression in these neuroendocrine areas was almost completely abolished, suggesting that the effect of GLP-1 on c-fos expression is mediated via specific receptors. A dual labeling immunocytochemical technique was used to identify the phenotypes of some of the neurons containing c-fos-immunoreactive nuclei. Approximately 80% of the CRH-positive neurons in the hypophysiotropic medial parvicellular part of the PVN coexpressed c-fos 90 min after icv GLP-1 administration. In contrast, very few (approximately 10%) of the vasopressinergic magnocellular neurons of the PVN/SON contained c-fos-positive nuclei, whereas approximately 38% of the magnocellular oxytocinergic neurons expressed c-fos-positive nuclei in response to GLP-1 administration. This study demonstrates that central administration of the anorectic neuropeptide GLP-1 activates the central CRH-containing neurons of the hypothalamo-pituitary-adrenocortical axis as well as oxytocinergic neurons of the hypothalamo-neurohypophysial tract. Therefore, we conclude that GLP-1 activates the hypothalamo-pituitary-adrenocortical axis primarily through stimulation of CRH neurons, and this activation may also be responsible for the inhibition of feeding behavior.
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PMID:Central administration of glucagon-like peptide-1 activates hypothalamic neuroendocrine neurons in the rat. 932 62

Induction of immediate-early genes (IEGs), such as c-fos, has been widely used to mark the activation of brain regions following different types of sexual stimulation and behavior. A relatively common set of hormone-concentrating basal forebrain and midbrain structures in female and male rodents is activated by copulatory stimulation, in particular, stimulation of sensory nerves that innervate the penis or vagina/cervix, olfactory or pheromonal stimuli, and conditioned sexual incentives. These regions include the preoptic area, lateral septum, bed nucleus of the stria terminalis, paraventricular hypothalamus, ventromedial hypothalamus, medial amygdala, ventral premammillary nuclei, ventral tegmentum, central tegmental field, mesencephalic central gray, and peripeduncular nuclei. Regions that do not contain classic intracellular steroid receptors, such as the ventral and dorsal striatum or cortex, are also activated. IEGs have also been colocalized with cytoplasmic proteins like GnRH and oxytocin, and have been used in conjunction with retrograde tracers to reveal functional pathways associated with different sexual behaviors. Steroid hormones can also alter the ability of sexual stimulation to induce IEGs. Despite the many similarities, some differences in IEG induction between sexes have also been found. We review these findings and raise the question of what IEG induction in the brain actually means for sexual behavior, that is, whether it indicates the perception of sexual stimulation, commands for motor output, or the stimulation of a future behavioral or neuroendocrine event related to the consequences of sexual stimulation. To understand the role of a particular activated region, the behavioral or neuroendocrine effects of lesions, electrical stimulation, drug or hormone infusions, must also be known.
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PMID:Implications of immediate-early gene induction in the brain following sexual stimulation of female and male rodents. 937 Feb 4


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