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)

Corticotropin releasing hormone (CRH) has been localized to interneurons of the mammalian cerebral cortex, but these neurons have not been fully characterized. The present study determined the extent of co-localization of CRH with glutamate decarboxylase (GAD) and calcium-binding proteins in the infant rat neocortex using immunocytochemistry. CRH-immunoreactive (ir) neurons were classified into two major groups. The first group was larger and consisted of densely CRH-immunostained small bipolar cells, predominantly localized to layers II and III. The second group of CRH-ir cells was lightly labeled and included multipolar neurons mainly found in deep cortical layers. Co-localization studies indicated that the vast majority of CRH-ir neurons, including both bipolar and multipolar types, was co-immunolabeled for GAD-65 and GAD-67. Most multipolar, but only some bipolar, CRH-ir neurons also contained parvalbumin, while CRH-ir neurons rarely contained calbindin or calretinin. These results indicate that virtually all CRH-ir neurons in the rat cerebral cortex are GABAergic. Furthermore, since parvalbumin is expressed by cortical basket and chandelier cells, the co-localization of CRH and parvalbumin suggests that some cortical CRH-ir neurons may belong to these two cell types.
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PMID:Co-localization of corticotropin-releasing hormone with glutamate decarboxylase and calcium-binding proteins in infant rat neocortical interneurons. 986 Feb 72

The testicular regulation of luteinizing hormone (LH) secretion in the adult rhesus monkey is mediated by an indirect action of testosterone to decelerate pulsatile gonadotrophin releasing hormone (GnRH) release. Whether this negative feedback action of testosterone involves regulation of GnRH gene expression is unknown. Therefore, the effect of bilateral orchidectomy on hypothalamic levels of the mRNA encoding this hypophysiotropic factor was examined. The feedback action of testosterone is generally considered to be mediated through non-GnRH cells, and the present experiment provided the opportunity to also examine testicular influences on mRNAs encoding putative hypothalamic factors implicated in the testicular regulation of LH secretion. Adult male rhesus monkeys were orchidectomized (n=5) or sham-orchidectomized (n=5) and killed 6 weeks later, after a castration-induced hypersecretion of LH was established. Separate preoptic and mediobasal hypothalamus containing areas were collected, and levels of GnRH mRNA, as well as those of mRNAs encoding pro-opiomelanocortin (POMC), the gamma-aminobutyric acid (GABA) synthesizing enzymes (glutamic acid decarboxylase 65 and 67; GAD65 and GAD67, respectively), neuropeptide Y, galanin and transforming growth factor (TGF)alpha, were quantified using RNase protection assay. Values were expressed in terms of optical density relative to that of cyclophilin mRNA levels. Bilateral orchidectomy produced a significant increase in GnRH mRNA levels that was restricted to the mediobasal hypothalamus and that was associated with a significant decrease in POMC, GAD65 and GAD67 mRNA levels in this region of the hypothalamus. In contrast, neuropeptide Y, galanin and TGFalpha mRNA levels were not affected by castration. These results indicate that, in the monkey, the deceleration of pulsatile GnRH release that is imposed by the testis, and presumably mediated by testosterone, is associated with a concomitant down regulation of GnRH gene expression in the mediobasal hypothalamus. They also support the notion that this hypothalamic feedback action may be mediated by POMC-and GABA-producing neurones in the mediobasal hypothalamus.
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PMID:Effects of orchidectomy on levels of the mRNAs encoding gonadotropin-releasing hormone and other hypothalamic peptides in the adult male rhesus monkey (Macaca mulatta). 1071 12

In aging brain, degeneration or functional impairment of the hippocampus has been connected with stress dysregulation, serving to disinhibit stress responses and allow for glucocorticoid hypersecretion and its attendant pathophysiology. Hippocampal dysfunction appears to be communicated to paraventricular hypothalamic corticotropin-releasing hormone neurons by way of subcortical GABAergic neurons. As such, hippocampal-hypothalamic relays are likely to play an important role in age-related stress dysfunction. To test this hypothesis, regulation of glutamic acid decarboxylase isoform mRNA was studied in young (3 months), middle aged (15 months) and aged (30 months) Fischer 344/Brown Norway F1 hybrid rats. Basal expression of glutamic acid decarboxylase (GAD) 65 mRNA was increased in the medial preoptic area and posteromedial bed nucleus of the stria terminalis (BST) in aged rats relative to both middle-aged and young groups. Unlike young or middle-aged animals, exposure to chronic intermittent stress decreased GAD65 mRNA levels in the medial preoptic area and posteromedial BST of aged rats. Thus, while aged rats show evidence of elevated basal GABA synthesis, chronic stress causes differential loss of GAD in hippocampal-PVN relays, consistent with reduced PVN inhibition.
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PMID:Differential regulation of forebrain glutamic acid decarboxylase mRNA expression by aging and stress. 1152 Apr 93

Prolonged social subjugation produces physiological indices of chronic stress in rats. In the current study, we examined the impact of social stress on glutamic acid decarboxylase (GAD) isoforms, corticotropin-releasing hormone (CRH) and vasopressin mRNA expression in forebrain stress circuitry, using the visible burrow system model of dominance-subordination. Subordinate male rats develop behavioral and neuroendocrine changes consistent with exposure to chronic stress, including marked loss of body weight and elevation of basal plasma corticosterone relative to dominant rats. Forebrain GAD65, GAD67, CRH and vasopressin mRNA expression in central stress-regulatory circuits were examined by in situ hybridization. Elevated CRH mRNA was observed in the oval nucleus of the bed nucleus of the stria terminalis (BST) of subordinate males. In contrast, GAD67 expression was decreased in the interfascicular nucleus of the BST in both the subordinate and dominant rats compared to non-burrow control rats. No changes in CRH, GAD or vasopressin were observed in amygdaloid nuclei, other BST nuclei or in the hypothalamic paraventricular nucleus. Collectively, these data suggest that exposure to the visible burrow system attenuates BST GAD expression regardless of social status, whereas the enhanced physiological responses to social stress seen in subordinates may be associated with enhanced CRH expression in the oval nucleus of the BST.
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PMID:Chronic social stress in the visible burrow system modulates stress-related gene expression in the bed nucleus of the stria terminalis. 1694 12

Chronic stress precipitates pronounced enhancement of central stress excitability, marked by sensitization of hypothalamic-pituitary-adrenocortical (HPA) axis responses and increased adrenocorticotropic hormone (ACTH) secretagogue biosynthesis in the paraventricular nucleus of the hypothalamus (PVN). Chronic stress-induced enhancement of HPA axis excitability predicts increased excitatory and/or decreased inhibitory innervation of the parvocellular PVN. We tested this hypothesis by evaluating chronic variable stress (CVS)-induced changes in total (synaptophysin), glutamatergic (VGluT2), GABAergic (GAD65), and noradrenergic (DBH) terminal immunoreactivity on PVN parvocellular neurons using immunofluorescence confocal microscopy. CVS increased the total PVN bouton immunoreactivity as well as the number of glutamatergic and noradrenergic immunoreactive boutons in apposition to both the corticotropin-releasing hormone (CRH)-immunoreactive cell bodies and dendrites within the parvocellular PVN. However, the number of GABAergic-immunoreactive boutons in the PVN was unchanged. CVS did not alter CRH median eminence immunoreactivity, indicating that CVS does not enhance CRH storage within the median eminence. Taken together, the data are consistent with a role for both glutamate and norepinephrine in chronic stress enhancement of HPA axis excitability. These changes could lead to an enhanced capacity for excitation in these neurons, contributing to chronic stress-induced hyperreactivity of stress effector systems in the brain.
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PMID:Chronic stress-induced neurotransmitter plasticity in the PVN. 1973 12