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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We demonstrate that granular cerebellar neurons express functional corticotropin-releasing hormone (CRH) receptors. Activation of these receptors with CRH receptor agonists leads to a dose-dependent increase in cyclic AMP (cAMP) levels with an apparent EC50 close to 10(-9) M. Using the c-fos protooncogene as a system to evaluate genomic effects of CRH, we show that activation of CRH receptors regulates gene expression at the transcriptional level. CRH rapidly induced c-fos mRNA accumulation. Genetic studies, using chimera genes containing human c-fos promoter sequences coupled to a chloramphenicol acetyltransferase (CAT) reporter gene, confirmed and extended this observation. When protein kinase A (PKA) was specifically inactivated by gene transfer of a mutated regulatory subunit of PKA lacking cAMP binding sites, CRH-stimulated c-fos transcription was suppressed but the increase in cAMP level was not affected, indicating a key role of PKA in mediating CRH-stimulated transcription. As CRH clearly modulates gene expression via the cAMP pathway, we analyzed the genomic effect of this neurohormone on a deleted c-fos-CAT construct containing only the cAMP-responsive element (CRE) and on a heterologous promoter construct bearing the minimal palindromic consensus CRE (core sequence TGACGTCA). These minimal cAMP-responsive genes are induced by CRH. These inductions are dependent on functional PKA. Taken together, our results demonstrate the presence of functional CRH receptors in primary cerebellar cultures. Activation of these receptors stimulates gene expression via the cAMP/PKA pathway and the transacting factor CREB (cAMP-responsive element binding protein).
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PMID:Characterization and genetic analysis of functional corticotropin-releasing hormone receptors in primary cerebellar cultures. 838 Apr 41

Vasopressin has been shown to be localized in specific central nervous system (CNS) sites. There is considerable evidence that it can act as a central neurotransmitter and it has been ascribed a variety of putative roles in the CNS. To identify those regions of the brain capable of responding to this peptide, 250 pmol vasopressin were infused into the lateral ventricle intracerebroventricular of conscious, handled male rats, and their brains processed for fos-immunohistochemistry 60 min later. Increases in fos-immunoreactivity, compared with cerebrospinal fluid-infused controls, were found in specific regions of the basal forebrain and brainstem: the central nucleus of the amygdala, ventrolateral septum, parvocellular divisions of the paraventricular nucleus of the hypothalamus, dorsal tuberal nucleus and locus coeruleus. Pre-infusion of 2500 pmol of a V1a antagonist prevented or reduced the expression of c-fos by intracerebroventricular vasopressin in all areas except the dorsal parvocellular paraventricular nucleus, implying that in most (but not all) areas the actions of vasopressin are mediated by the V1a receptor. Central administration of vasopressin had no effect on plasma corticosterone levels. Vasopressin and corticotropin-releasing factor act synergistically on the anterior pituitary to cause release of adrenocorticotropic releasing hormone and have corresponding synergistic interactions on behaviour. Infusion of 250 pmol corticotropin releasing factor produced a similar but not identical pattern of fos-like immunoreactivity to that of vasopressin. Activation of the parabrachial nucleus was observed, but there was no significant effect on the lateral septum and apparent increases in the medial parvocellular division of the paraventricular nucleus and locus coeruleus were not significant. Corticotropin releasing factor also caused a marked rise in plasma corticosterone. When the two peptides were infused together (125 pmol each) no evidence for synergy was found, in terms of the number of neurons activated to express c-fos. The induction of differential patterns of fos-like immunoreactivity by vasopressin and corticotropin-releasing factor in specific regions of the limbic forebrain and brainstem has implications for the individual roles they play in the CNS.
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PMID:Expression of c-fos in restricted areas of the basal forebrain and brainstem following single or combined intraventricular infusions of vasopressin and corticotropin-releasing factor. 848 52

Exposure to an antigen causes significant endocrine changes, some of which in turn affect immune functioning. Proteins produced by activated immune cells, cytokines, act as messengers between the immune and the endocrine systems, and convey to the brain the occurrence of immune activation. We have investigated the ability of interleukin 1 (IL-1) alpha and beta to alter endocrine functioning in the adult rat. Acute peripheral injection of IL-1 alpha or beta causes dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and corticosterone secretion. These changes are primarily dependent upon increased release of corticotropin-releasing factor (CRF) into the portal circulation, and recent studies have indicated that the paraventricular nucleus (PVN) of the hypothalamus is the main source of this CRF. This conclusion is based on our finding that intravenous injection of IL-1 increases CRF biosynthesis in the PVN, and that lesion of this hypothalamic area interferes with IL-1's stimulatory action on ACTH secretion. Indomethacin partially reverses the effect of IL-1, suggesting that increased prostaglandin synthesis plays some part in this activation. Administration of IL-1 beta into the brain, but not into the general circulation, interferes with secretion of luteinizing hormone (LH) and ovulation through mechanisms involving endogenous opiates. Because neither CRF antagonists, nor lesions of the PVN, alter the inhibitory effect of IL-1 on LH release, CRF perikarya in the PVN do not appear to be involved in this phenomenon. Central administration of IL-1 beta strongly increases c-Fos immunoreactivity in the PVN, mainly within CRF neurons. Infusion of IL-1 beta into the PVN does not induce measurable changes in release of gonadotropin-releasing hormone (GnRH), but infusion of IL-1 directly into the median preoptic area (MPOA), a region rich in GnRH perikarya, markedly decreases GnRH secretion in rats bearing a push-pull cannula in the median eminence. Furthermore, central administration of IL-1 beta during the critical phase of pro-oestrus (1600-1930) also inhibits the expression of c-fos in GnRH cell bodies in the MPOA. Thus, we suggest that IL-1 interferes with reproductive functioning through a direct action at the level of the MPOA. These results indicate that circulating cytokines can alter the activity of the hypothalamo-pituitary-adrenal axis by increasing CRF release, probably through both immediate stimulation of CRF terminals within the median eminence and stimulation of CRF synthesis in the PVN. In contrast, cytokine-induced changes in LH and GnRH secretion are mediated through pathways lying primarily beyond the blood-brain barrier.
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PMID:Mechanisms mediating the effects of cytokines on neuroendocrine functions in the rat. 849 Oct 87

The POMC gene, encoding a hormonal precursor protein, is primarily expressed in the pituitary in a tissue-specific manner. The POMC gene is transcriptionally regulated by a variety of hormones and neuropeptides and the second messengers cAMP and Ca++. Using the corticotrope-derived AtT20 cell line, we have previously shown that overexpression of cFos stimulates POMC transcription. The aim of this work was to analyze whether cFos directly interacts with the POMC gene in basal and corticotropin-releasing hormone (CRH) stimulated cells. Using progressively deleted POMC promoter sequences or heterologous promoter constructs coupled to the chloramphenicol acetyl transferase reporter gene, we demonstrate the existence of a major cFos- responsive sequence within the first exon of the POMC gene. This sequence, TGACTAA, appears functionally indistinguishable from the canonical AP1 binding site. When fused to a minimal promoter, this sequence confers inducibility by cFos and CRH. Gel shift analyses with CRH-stimulated AtT20 nuclear extracts or in vitro synthesized proteins revealed that this sequence efficiently binds Fos and Jun. Expression of c-fos anti-sense mRNA reduced CRH-stimulated POMC transcription, thus indicating that, at least in part, cFos mediates the effect of CRH on POMC transcription. However, deletion of this major exonic AP1 site from the POMC constructs greatly reduced the effect of c-fos overexpression but did not suppress POMC stimulation by CRH, indicating that CRH stimulates POMC transcription by one or more cFos-independent mechanism(s).
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PMID:Corticotropin-releasing hormone stimulates proopiomelanocortin transcription by cFos-dependent and -independent pathways: characterization of an AP1 site in exon 1. 859 20

Systemic hypoxia stimulates the release of vasopressin (VP) and adrenocorticotropin hormone (ACTH). To examine the involvement of catecholamine cell groups of the ventrolateral medulla (VLM) in the neuroendocrine responses, we have used the c-fos activity mapping technique to compare the effects of hypoxia on VLM catecholamine cells to those on neurosecretory VP and putative corticotropin releasing factor (CRF) containing cells. A limited degree of catecholamine cell activation was evident at predominantly mid-VLM levels at 12% oxygen in the inspired air. Further reduction in inpsirate oxygen levels enhanced recruitment of caudally located VLM catecholamine cells considered to form part of the A1 noradrenergic cell group. Threshold for activation of VP and putative CRF cells occurred at the 10% oxygen level. Unexpectedly, this stimulus also activated neurosecretory oxytocin (OT) cells. With increasing hypoxic severity the number of activated supraoptic VP and OT cells was not significantly different to that observed at the 10% level. However, paraventricular neuroendocrine responses continued to increase with putative CRF containing cells of the medial parvocellular zone having nearly double the level of activity (as measured by the number of cells within this region displaying Fos-like immunoreactivity; FLI) at 6% compared to that apparent to the 10% level of hypoxia. Paraventricular VP cells displaying FLI were also increased at the most severe levels of hypoxia but this effect was much less marked than the medial parvocellular response. Consistent with a role for VLM catecholamine cells in generation of neuroendocrine cell responses to hypoxia, unilateral VLM lesions, restricted to the caudal two thirds of the catecholamine cell column, resulted in significant reductions in the responses of all three cell types. These results, in addition to establishing a role for VLM catecholamine cells in neuroendocrine cell responses to systemic hypoxia, have important general implications for catecholamine cell group involvement in neuroendocrine regulation.
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PMID:Role of ventrolateral medulla catecholamine cells in hypothalamic neuroendocrine cell responses to systemic hypoxia. 861 35

Immediate-early genes (IEGs) are widely used to mark endocrine hypothalamic neurons that are activated in response to stress, yet their relationship to the transcriptional control of relevant effector molecule expression is unclear. Acute ether stress provokes increased adrenocorticotropic hormone (ACTH) and corticosterone secretion that peaks at 5 and 30 min, respectively, after the challenge. Using probes complementary to intronic sequences of genes encoding ACTH secretagogues in parvocellular neurosecretory neurons of the paraventricular nucleus, we found these events to be accompanied by rapid and transient increases in corticotropin-releasing factor heteronuclear RNA (CRF hnRNA; peak at 5 min) and by a delayed upregulation of arginine vasopressin (AVP) hnRNA (120 min). To identify candidate mechanisms regulating peptide expression, we followed the timing of ether effects on representatives of three transcription factor classes: IEGs [c-fos and nerve growth factor I-B (NGFI-B)], a POU-domain factor (Brn-2), and the cAMP response element-binding protein (CREB), using antisera specific to its transcriptionally active, phosphorylated form (pCREB). After ether exposure, c-fos and NGFI-B mRNA induction were maximal at 30--60 min, whereas Fos protein peaked at 60--120 min. Brn-2 mRNA was expressed constitutively in the PVH and was unresponsive to stress. By contrast, pCREB was induced in parvocellular neurons with a time course parallel to that of CRF hnRNA expression. Stress-induced transcriptional activation of the CRF and AVP genes in hypophysiotropic neurons follows distinct time courses that are compatible with control mechanisms involving phosphorylation events and de novo protein synthesis, respectively.
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PMID:Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons. 861 92

The paraventricular nucleus of the hypothalamus (PVN) serves as the origin of the final common pathway in the secretion of glucocorticoid hormones in response to stress. Various stress-related inputs converge upon the cells of the medial parvocellular division of the PVN. These neurons, which synthesize and release corticotropin-releasing hormone, arginine vasopressin, and other secretagogues, are responsible for a cascade of events which culminates in the adrenocorticotropin-induced release of corticosteroids from the adrenal cortex. Previous data have suggested complex afferent regulation of PVN neurons, although the neuronal pathways by which the effects of stress are mediated remain to be fully disclosed. The present experiment sought to identify forebrain areas potentially involved in afferent regulation of the PVN in response to an acute stressor. Discrete injections of the retrograde tracer Fluoro-gold were delivered to the PVN, and rats were subsequently subjected to an acute swim stress. Brains were processed immunocytochemically for the simultaneous detection of the tracer and Fos, the protein product of the immediate early gene c-fos, utilized as a marker for neuronal activation. The majority of Fluoro-gold/Fos labeled neurons were detected in the parastrial nucleus, the medial preoptic area, the anterior hypothalamic area, the dorsomedial hypothalamic nucleus and adjacent posterior hypothalamic area, and, to a lesser extent, the supramammillary nucleus. These findings are discussed in relation to neural pathways mediating activation and inhibition of the hypothalamic-pituitary-adrenocortical axis.
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PMID:Fos expression in forebrain afferents to the hypothalamic paraventricular nucleus following swim stress. 872 95

Using cultured bovine adrenal fasciculata cells (BAC), we investigated the effects of two hormones, corticotropin (ACTH) and angiotensin II (Ang-II) and two growth factors, insulin-like growth factors I (IGF-I) and transforming growth factor beta 1 (TGF beta 1), on the mRNA levels of nuclear proto-oncogenes of the Fos and Jun families and on the mRNA levels of genes expressed in BAC coding for ACTH and AT1 receptors, cytochrome P450scc and P450 17 alpha and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). ACTH and IGF-1 increased c-fos and jun-B mRNA levels early with later increases in the levels of mRNA for the ACTH receptor and the three steroidogenic enzymes, and enhanced steroidogenic responses to both ACTH and Ang-II. In contrast, Ang-II increased mRNA coding for the three proto-oncogenes (cfos, c-jun, and jun-B), decreased those for P450 17 alpha and 3 beta-HSD, and caused marked homologous and heterologous steroidogenic desensitization. TGF beta 1 increased only jun-B mRNA and markedly reduced BAC-differentiated functions and steroidogenic responsiveness to both ACTH and Ang-II. The long-term effects of ACTH on human adrenal fasciculata cells were comparable with those observed in BAC, whereas the long term effects of Ang-II and TGF beta 1 were different from those observed in BAC. Whether these species-specific differences are related to a different effect of these factors on proto-oncogene expression is not yet known.
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PMID:Regulation of primary response and specific genes in adrenal cells by peptide hormones and growth factors. 873 96

A marked expression of the c-fos proto-oncogene has been recently reported in cells of the anterior lobe of the pituitary gland in rats subject to electroacupuncture or noxious thermal stimulation under pentobarbital anaesthesia. The present study was undertaken to identify the activated pituitary cells. Following both kinds of stimulation, most Fos-immunoreactive anterior lobe cells showed colocalization with adrenocorticotropic hormone or beta-endorphin immunoreactivity. No c-fos expression occurred in pituitary cells immunoreactive for growth hormone, prolactin, luteinizing hormone, or thyrotropin-stimulating hormone. A marked rise of adrenocorticotropic hormone and beta-endorphin concentrations occurred in plasma. In the hypothalamus, c-fos expression was increased in the mediobasal nuclei-namely, the arcuate nucleus-and in the paraventricular nucleus, but more in the former. It is suggested that somatosensory noxious input, or the partly noxious input evoked by electroacupuncture, activate the hypothalamo-pituitary-adrenocortical axis as in common forms of stress, but with a specific activation of the mediobasal hypothalamic nuclei and no stimulation of intermediate lobe cells. Opiate release from the pituitary gland may contribute to acupuncture analgesia or the intrinsic antinociceptive reactions triggered by noxious stimulation.
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PMID:Activation of anterior lobe corticotrophs by electroacupuncture or noxious stimulation in the anaesthetized rat, as shown by colocalization of Fos protein with ACTH and beta-endorphin and increased hormone release. 873 78

We have previously shown in dehydrated rats that cellular levels of the mRNAs encoding the precursor peptides for corticotropin-releasing hormone and neurotensin/neuromedin N significantly increase in a restricted region of the lateral hypothalamic area (Watts, 1992, Brain Res. 581:208-216). The experiments reported here address the role that forebrain osmosensitive cells groups or regions associated with autonomic regulation play in developing this mRNA response. The first experiment showed that unilateral knife cuts placed between the rostral forebrain and the lateral hypothalamic area (LHA) will unilaterally attenuate the mRNA response in the LHA to dehydration. In a second experiment, small injections of the retrograde tracer Fluorogold into the region of the LHA containing these mRNAs revealed a direct input from the osmosensitive median preoptic nucleus and subfornical organ and from the fusiform nucleus of the bed nuclei of the stria terminalis, which is part of a complex of cell groups associated with autonomic regulation. We found that at least 30% of the neurons in the median preoptic nucleus and subfornical organ and 14% of the neurons in the fusiform nucleus of the bed nuclei of the stria terminalis that project to the LHA responded to a rapid increase in plasma osmolality with increased c-fos mRNA levels. In the final experiment, injections of Fluorogold into the LHA were made simultaneously with ipsilateral rostral knife cuts. Here the numbers of neurons accumulating Fluorogold in the median preoptic nucleus, subfornical organ, and the fusiform nucleus were all significantly decreased concomitantly with attenuated mRNA responses in the LHA to dehydration. We conclude that the LHA receives direct and functional projections from the median preoptic nucleus, subfornical organ, and the fusiform nucleus. These projections appear capable of mediating a substantial part of the response of peptidergic mRNAs in the LHA to dehydration.
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PMID:Mediation of dehydration-induced peptidergic gene expression in the rat lateral hypothalamic area by forebrain afferent projections. 880 32


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