Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insulin-like growth factor I (IGF-I) gene generates by alternative splicing two IGF-I messenger RNAs (mRNAs) coding for IGF-I prehormones with different E domain sequences. In rats, these two mRNAs differ by the presence (IGF-IB) or absence (IGF-IA) of a 52-bp insert in the E domain coding region. The purpose of this study was to investigate the effect of nutritional perturbation on IGF-IA and -IB expression in rat liver. Northern blot analysis of liver mRNA revealed that the 1.5-1.9 kb and 0.9-1.2 kb IGF-I mRNA species were decreased in rats fasted for 48 h compared with either fasted-refed (48 h of each) or control-fed rats (each, P < 0.01), whereas the 7.5 kb IGF-I mRNA was decreased only when compared with the fasted-refed animals. Using semiquantitative RT-PCR, the IGF-IA transcript (114 bp amplicon) was not altered, whereas the IGF-IB transcript (166 bp amplicon) was decreased in fasted rats compared with the other two groups (both P < 0.01). We confirmed the RT-PCR results by RNase protection assay (RPA), observing that the IGF-IA (224 and 100 bases protected) was not decreased and that the IGF-IB transcript (376 bases protected), accounting for only 23% of the total IGF-I transcripts of control fed rats, was decreased by fasting. Because the results from RT-PCR and RPA do not necessarily predict full-length translatable mRNA, we subjected hepatic IGF-I transcripts to in vitro translation, and we immunoprecipitated IGF-IA and -IB prehormones. Both prehormones were translated principally from exon 1-containing mRNAs, with molecular weights of about 17K and 18K, representing 80% and 20% of the total IGF-I prehormones observed in control fed rats, respectively. Both peptides were reduced in fasted rats compared with controls (P < 0.01), and refeeding restored both. By immunoblotting of the protein extract from liver of fasted rats, IGF-IA was decreased by 77% compared with control-fed animals. Refeeding returned IGF-IA to normal. The lack of reduction of IGF-IA transcript at the alternative splice site suggests that posttranscriptional mechanisms are responsible for the reduction in steady-state IGF-I mRNAs that occurs during fasting. Additionally, we present evidence that biosynthesis of IGF-IA and -IB prehormones by liver is impaired at a posttranscriptional level.
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PMID:Effect of fasting on insulin-like growth factor (IGF)-IA and IGF-IB messenger ribonucleic acids and prehormones in rat liver. 923 57

Insulin-like growth factor-1 (IGF-1) is considered to play an important role during ovarian development and function. Because ethanol (ETOH) is a gonadal toxin in men, as well as male and female rats, we hypothesized that this drug may be having detrimental effects in the ovary by altering the intraovarian actions of IGF-1. In support of this notion, the present study was undertaken to examine the chronic effects of ETOH on the ovarian IGF-1 system in prepubertal female rats. Each rat was implanted with a gastric cannula on day 24 and began receiving either a control or ETOH liquid diet on day 29. The animals were killed on day 34, confirmed to be in the late juvenile stage of development, and their ovaries and blood were collected. Using an RNase protection assay, we determined the expression of mRNAs encoding IGF-1 and the Type 1 IGF receptor in the ovaries of control and ETOH-treated rats. Results indicate that the ETOH-treated rats showed an increase in the ovarian expression of IGF-1a (p < 0.0001) and IGF-1b (p < 0.001) mRNA, the two alternatively spliced forms of the IGF-1 gene. Conversely, ovarian IGF-1 protein levels were depressed (p < 0.05) in ETOH-treated rats as determined by radioimmunoassay. Furthermore, ETOH-treated rats showed a decrease (p < 0.01) in the expression of Type-1 IGF receptor mRNA with a subsequent decrease (p < 0.05) in the ovarian levels of IGF-1 receptor protein, as determined by Western blot analysis. Also, using Western immunoblotting, we determined increases in immunoreactive IGF-binding proteins-3 (p < 0.05) and 5 (p < 0.01), but not 4, in ETOH-treated rats as compared with controls. Furthermore, we observed a concomitant decrease (p < 0.01) in the serum levels of estradiol. These results demonstrate for the first time that chronic ETOH administration is capable of altering the prepubertal intraovarian IGF-1 signaling system. We suggest that, at least in part, these effects contribute to altered prepubertal ovarian function after chronic exposure to ETOH.
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PMID:Effects of ethanol on the intraovarian insulin-like growth factor-1 system in the prepubertal rat. 1006 59


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