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

The adrenocorticotropic hormone (ACTH) inhibits the growth of Y1 mouse adrenocortical tumor cells as well as normal adrenocortical cells in culture but stimulates adrenocortical cell growth in vivo. In this study, we investigated this paradoxical effect of ACTH on cell proliferation in Y1 adrenal cells and have unmasked a growth-promoting effect of the hormone. Y1 cells were arrested in the G1 phase of the cell cycle by serum starvation and monitored for progression through S phase by measuring [3H]thymidine incorporation into DNA and by measuring the number of nuclei labeled with bromodeoxyuridine. Y1 cells were stimulated to progress through S phase and to divide after a brief pulse of ACTH (up to 2 h). This effect of ACTH appeared to be cAMP independent, since ACTH also induced cell cycle progression in Kin-8, a Y1 mutant with defective cAMP-dependent protein kinase activity. The growth-promoting effect of ACTH in Y1 was preceded by the rapid activation of p44 and p42 mitogen-activated protein kinases and by the accumulation of c-FOS protein. In contrast, continuous treatment with ACTH (14 h) inhibited cell cycle progression in Y1 cells by a cAMP-dependent pathway. The inhibitory effect of ACTH mapped to the midpoint of G1. Together, the results demonstrate a dual effect of ACTH on cell cycle progress, a cAMP-independent growth-promoting effect early in G1 possibly mediated by mitogen-activated protein kinase and c-FOS, and a cAMP-dependent inhibitory effect at mid-G1. It is suggested that the growth-inhibitory effect of ACTH at mid-G1 represents an ACTH-regulated check point that limits cell cycle progression.
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PMID:Unmasking a growth-promoting effect of the adrenocorticotropic hormone in Y1 mouse adrenocortical tumor cells. 936 63

Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) are synergistically interacting ACTH secretagogues that are co-expressed by parvocellular neurosecretory neurons of the hypothalamic paraventricular nucleus (PVH). To shed light on the mechanisms that mediate the stress-induced transcriptional activation of these neuropeptide genes, quantitative hybridization histochemical methods were used to assess the effects of systemic treatment with the protein synthesis inhibitor, cycloheximide, on the ether stress-induced upregulation of primary CRF and AVP transcripts, in vivo. Pretreatment with cycloheximide prevented the induction of FOS, but not CREB phosphorylation, normally seen in response to acute ether exposure, and significantly attenuated the stress-induced rise in AVP, but not CRF, heteronuclear RNA expression in the parvocellular division of the PVH. These results support the view that distinct molecular mechanisms govern the expression of the two principal corticotropin-releasing factors, in vivo.
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PMID:Protein synthesis blockade differentially affects the stress-induced transcriptional activation of neuropeptide genes in parvocellular neurosecretory neurons. 952 53

In rats of both sexes, mating stimulates neuronal activity in forebrain areas that are also activated by stress. Hypothalamic cells in the arcuate (ARC) and paraventricular (PVN) nuclei synthesize hormones or peptides whose levels are altered by adrenalectomy. In this experiment, we examined whether the mating-induced expression of c-FOS in the forebrain is altered by adrenalectomy (Adx) in female rats. Ovariectomized females were adrenalectomized (Adx) or sham-operated (Sham), hormone-primed and mated 2 weeks after surgery. They received 15 intromissions (15I), 5 intromissions (5I) or 15 mounts without intromission (MO) from a male or were taken directly from their home cage (HC). Two hours after mating, rats were perfused with paraformaldehyde and their brains were collected and stained immunocytochemically for FOS protein. FOS-immunoreactive (FOS-IR) cells in the posterodorsal medial amygdala (MePD), bed nucleus of stria terminalis (BNST), ventromedial hypothalamus (VMH), medial preoptic area (mPOA), ARC and PVN were counted bilaterally. In Sham animals, intromissions produced significant increases in FOS above HC levels. In Adx animals, mating increased FOS activity in all areas. However, responses to 5I and 15I differed between Sham and Adx groups. In all areas, Shams showed either the highest FOS response following 15I or levels which were equivalent after 5I and 15I. In Adx animals, the greatest number of FOS-positive cells occurred after 5I, with the 15I group showing significant suppression of FOS below 5I levels in the VMH, mPOA, ARC and PVN. These results demonstrate that the adrenal modulates FOS responses to mating in the female rat and suggest that adrenal secretory products normally may decrease sensitivity to low levels of mating stimulation. These effects may be due to increased corticotropin-releasing hormone (CRH) or beta-endorphin in the hypothalamus after adrenalectomy.
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PMID:c-FOS expression in the forebrain after mating in the female rat is altered by adrenalectomy. 1280 76

The present study was conducted to investigate the effects of treadmill running on the corticotropin-releasing hormone (CRH), CRH receptor type 1 (CRH-R1) and CRH-binding protein (CRH-BP) in the brain of rats that were killed either at rest, immediately after 60 min of treadmill running, or 180 min following a 60-min session of intensive exercise. The expression of the neuronal activity marker c-FOS was also determined in the three conditions of this study. The levels of c-FOS mRNA immediately following running were high in the cortex, caudate-putamen, lateral septum, bed nucleus of the stria terminalis, dorsal and medial thalamus, hypothalamus, pontine nuclei, locus coeruleus and hypoglossal nucleus. In most brain regions investigated, excluding the locus coeruleus and the cingulate cortex, c-FOS mRNA expression returned to control levels after 2 h of recovery. The highest concentration of cells co-expressing the protein Fos and CRH mRNA neurons was found in the parvocellular part of the paraventricular nucleus, which also expressed CRH heteronuclear RNA and CRH-R1 mRNA. The medial preoptic area (MPOA), the medial mammillary nucleus and the posterior hypothalamic as well as the somatosensory cortex, the medial geniculate nucleus, the reticulotegmental nucleus, and Barrington's nucleus also co-expressed Fos and CRH mRNA. The expression of CRH-BP gene was induced in the MPOA following running. In summary, the present study demonstrates that treadmill running leads to a strong expression of c-FOS mRNA that is widely distributed throughout the brain. c-FOS mRNA was found in structures of the somatosensory and somatomotor systems, indicating that these regions were activated during exercise. The pattern of distribution of c-FOS mRNA showed similarities with that triggered by neurogenic and systemic stresses. The present results also indicate that treadmill running can strongly activate the hypophysiotropic CRH system, which suggests, in agreement with the pattern of c-FOS mRNA distribution, that treadmill running has a strong stress component.
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PMID:Effects of treadmill running on brain activation and the corticotropin-releasing hormone system. 1284 25

Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by quantitative PCR. In situ hybridization histochemistry of endogenous Pomc mRNA and immunohistochemical analysis of eGFP revealed that POMC is primarily localized within the caudal NTS. Neurochemical analysis indicated that POMCNTS is not co-expressed with tyrosine hydroxylase (TH), glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), brain-derived neurotrophic factor (BDNF), nesfatin, nitric oxide synthase 1 (nNOS), seipin, or choline acetyltransferase (ChAT) cells, whereas 100% of POMCNTS is co-expressed with transcription factor paired-like homeobox2b (Phox2b). We observed that 20% of POMCNTS cells express receptors for adipocyte hormone leptin (LepRbs) using a PomceGFP:LepRbCre:tdTOM double-reporter line. Elevations in endogenous or exogenous leptin levels increased the in vivo activity (c-FOS) of a small subset of POMCNTS cells. Using ex vivo slice electrophysiology, we observed that this effect of leptin on POMCNTS cell activity is postsynaptic. These findings reveal that a subset of POMCNTS cells are responsive to both changes in energy status and the adipocyte hormone leptin, findings of relevance to the neurobiology of obesity.
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PMID:Neurochemical Characterization of Brainstem Pro-Opiomelanocortin Cells. 3216 24