Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prodynorphin (Prodyn)-derived peptides are synthesized in a subset of gonadotrope cells and released concomitantly with LH and FSH, and their levels in the rat adenohypophysis are influenced by the gonadal steroid environment. In several hormonal systems, factors that affect peptide levels may modulate the transcription of messenger RNA (mRNA) encoding for the target gene. Therefore, the present study was designed to investigate the effects of gonadal ablation and estrogen replacement on changes in steady state levels of anterior pituitary Prodyn mRNA and on the transcription rate in the adult female rat. The antiestrogen tamoxifen was employed for further exploring the relationships between estrogens and dynorphin (dyn)-related peptides. Adopting a solution hybridization-ribonuclease protection assay, steady state levels of Prodyn mRNA doubled in 2-week ovariectomized (OVX) rats, in parallel with a 3-fold increase in immunoreactive dyn-A-(1-17)-like material (irdyn-A). Estradiol (E2) replacement through sc SILASTIC implants for 1, 3, 7, and 14 days, which produces serum E2 levels between 25-35 pg/ml, restored in a time-dependent manner mRNA and peptide concentrations to values in sham-OVX rats. A significant decrease was observed after 3 days, and after 7 days, the effect was maximal. Tamoxifen (250 micrograms/kg.day, sc) administered simultaneously antagonized the action of E2 on Prodyn gene expression. Tamoxifen administered without E2 for 7 or 14 days significantly raised anterior pituitary levels of Prodyn mRNA and ir-dyn-A. To establish whether E2 and tamoxifen exert their effects on adenohypophyseal Prodyn mRNA by influencing the transcriptional activity of this gene, an in vitro transcriptional elongation assay was performed on nuclei from the anterior pituitary. The transcriptional rate of the Prodyn gene was significantly increased in 2-week OVX rats. Prodyn mRNA synthesis was suppressed in OVX rats exposed to E2, an effect antagonized by tamoxifen administered concomitantly. The antiestrogen administered alone for 14 days further elevated the transcriptional rate of Prodyn mRNA induced by gonadal ablation. In conclusion, E2 down-regulated the synthesis of Prodyn-derived peptides in adenohypophyseal cells. The antiestrogen tamoxifen antagonized the effect of E2 and, when chronically administered to OVX rats, further elevated the postcastrational rise in Prodyn gene expression.
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PMID:Estrogen regulation of prodynorphin gene expression in the rat adenohypophysis: effect of the antiestrogen tamoxifen. 789 68

Dynorphin, an opioid peptide, is thought to play an important role in the modulation of nociceptive neural networks at the level of the spinal cord. Fos protein is involved in the transcriptional regulation of the dynorphin gene. Although several studies have been carried out on dynorphin gene expression by noxious somatic stimuli, few have evaluated the effect of noxious visceral stimuli on the expression of dynorphin gene. In the present studies we analysed the expression of the dynorphin gene mediated by a noxious visceral stimulus in a rat model by exposure of abdominal tissue to carrageenan. Expression of preprodynorphin and c-fos mRNAs in the spinal cord neuron was examined using ribonuclease protection assays. After inflammation, a rapid increase in the levels of c-fos mRNA in the thoracic spinal cord was observed. c-fos mRNA levels rose within 30 minutes after injection, and remained elevated for 1 hour, subsequently falling to control levels. In contrast, preprodynorphin mRNA began to increase from 30 minutes after injection and remained elevated for at least 2 days. In situ hybridization with alpha 35S-labeled cRNA probe demonstrated that in the lower thoracic spinal cord preprodynorphin mRNA was expressed in dorsal horn neurons. In celiac ganglia, both preprodynorphin and c-fos mRNAs were not detected. In the peripancreatic abdominal tissue, there was acute severe inflammation consisting of necrosis and marked polymorphonuclear leucocytic infiltration. These data demonstrate that after abdominal tissue inflammation, activation of dynorphin biosynthesis occurred in thoracic spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Expression of preprodynorphin mRNA in the spinal cord after inflammatory abdominal stimulation in rats]. 790 75

The opioid peptide dynorphin (DYN) is expressed normally at high levels in dentate gyrus granule cells in hippocampus and in neurons in entorhinal and neocortex. In the present study, ribonuclease protection and in situ hybridization analyses were used to examine preproDYN mRNA expression in hippocampus and neocortex following recurrent limbic seizure induced by a unilateral electrolytic lesion of the dentate gyrus hilus. In this paradigm, electrographic seizures within hippocampus recur intermittently from 1.6 to 12 h following the hilus lesion (HL). Solution hybridization-ribonuclease protection analysis of preproDYN mRNA levels in hippocampal dentate gyrus/CA1 samples from rats sacrificed 6 and 12 h following HL revealed an approximate 6-fold increase above control values at both times. PreproDYN mRNA levels returned toward control values by 24 h post-HL, were suppressed up to 10-fold below control values at 48 and 96 h post-HL, and then returned to control levels by 10 days post-HL. In situ hybridization analyses confirmed the biphasic nature of seizure-induced changes in preproDYN expression specifically within dentate gyrus granule cells. Additionally, these latter studies demonstrated that seizures induce expression of preproDYN mRNA in a small population of neurons within stratum pyramidale CAL Transient increases in preproDYN mRNA were also detected in subiculum and entorhinal cortex. However, in neocortex hybridization of preproDYN mRNA remained constant through 96 h post-HL. These findings of biphasic seizure-induced alterations in preproDYN mRNA expression can be contrasted with previously described changes in gene expression following limbic seizure activity and suggest that different cellular mechanisms regulate expression of colocalized hippocampal neuropeptides such as dynorphin, Metenkephalin, and neuropeptide Y.
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PMID:Biphasic response of hippocampal dynorphin expression following recurrent limbic seizure. 1991 48