Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The insulin-like growth factors (IGFs) may be important autocrine and paracrine mediators of organ growth. We used solution-hybridization/ribonuclease protection assays to examine IGF-I and IGF-II mRNA abundance during hypertrophy or the rat adrenal gland induced by unilateral adrenalectomy or by adrenocorticotropic hormone (ACTH) infusion. Adrenal IGF-I mRNA did not change during the period of rapid organ growth at 18 or 66 h after unilateral adrenalectomy. ACTH infusion induced a time- and dose-dependent decrease in adrenal IGF-I mRNA despite significant increases in gland size. IGF-II mRNA also remained unchanged after unilateral adrenalectomy and decreased after ACTH infusion, to a greater extent than IGF-I mRNA. Liver IGF-I mRNA did not change with ACTH exposure, indicating an effect specific to the adrenal. We also measured adrenal P450scc mRNA as a marker of steroidogenic capacity. P450scc mRNA was unchanged after unilateral adrenalectomy and increased with ACTH infusion. Thus IGF-I and IGF-II mRNAs respond in parallel, but in different fashions with different stimuli for adrenal growth. The decrease in IGF mRNA after exposure to ACTH may be a factor in the ACTH-induced inhibition of compensatory hypertrophy after unilateral adrenalectomy.
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PMID:Rat insulin-like growth factor-I and -II mRNAs are unchanged during compensatory adrenal growth but decrease during ACTH-induced adrenal growth. 226 16

Insulin-like growth factor II is a growth factor important in fetal development. Several cancer tissues and cell lines have been reported to express IGF-II and rat IGF-II is mitogenic for breast cancer cell lines. Using Northern analysis and ribonuclease protection assays, IGF-II mRNA was detected in normal fibroblasts and in the established breast cancer cell line, T47D. In this cell line, steady state levels of IGF-II message were increased by treatment with estradiol. 10 nM IGF-II, purified from human serum, was mitogenic for breast cancer cell lines. In vitro, IGF-II may act as an autocrine growth factor for some cell lines. RNA derived from breast cancer, pathologically normal breast tissue, and benign breast disease also contained IGF-II mRNA. When paired samples of normal and cancer tissue were obtained from the breast of the same patient, the level of IGF-II mRNA expression in the normal tissue was at least that found in the cancer. This is consistent with previous observations that show IGF-II is expressed in mesenchyme. These findings suggest that in breast cancer IGF-II is produced by stromal tissue elements and potentially by the malignant epithelial cells. Therefore, IGF-II may function as an autocrine or a paracrine growth factor in different breast tumors.
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PMID:Insulin-like growth factor II mRNA expression in human breast cancer. 318 80

Previous studies have shown that insulin-like growth factors (IGF-I and IGF-II) stimulate mitogenic activity in human endometrial stromal cells. In the present study, we have investigated the expression of IGF-I and -II mRNA to ascertain any autocrine growth-promoting effect in this system. Northern blot analysis revealed that endometrial stromal cells express multiple sizes of IGF-I and -II transcripts. The effect of progestin and antiprogestin was studied during decidualization of endometrial stromal cells in long-term culture. Solution hybridization and a ribonuclease protection assay of control cells revealed that the level of IGF-I mRNA was low, whereas IGF-II mRNA was always abundant. Medroxyprogesterone acetate (MPA) stimulated the expression of IGF-I mRNA > 4-fold in predecidualized cells during the first 10 days of culture. IGF-I mRNA decreased to basal level in prolonged culture when cells were decidualized. In contrast, MPA suppressed the IGF-II mRNA level by 60% in predecidualized cells, but IGF-II mRNA was highly expressed after 20 days of incubation with MPA (5-fold increase from Days 5-10 to Day 20 of culture). In progestin-pretreated cells, addition of the antiprogestin RU486 for 1-4 days reduced IGF-I mRNA by 50-90%. RU486 reversed the suppressive effect of MPA and increased IGF-II mRNA. This study indicates that progestin and antiprogestin differentially regulate IGF-I and IGF-II mRNA levels in human endometrial stromal cells.
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PMID:Progestin and antiprogestin differentially regulate the expression of insulin-like growth factors (IGF-I and IGF-II) messenger ribonucleic acid in human endometrial stromal cells. 749 87

This study examined the hypothesis that during aging insulin-like growth factor (IGF) mRNAs are reduced in skeletal muscle. IGF-I, IGF-II, and IGF-binding protein-5 (IGFBP-5) mRNAs were measured with a ribonuclease protection assay in the gastrocnemius of specific pathogen-free Fischer-344 rats. We hypothesized that IGF-I, IGF-II, and IGFBP-5 mRNA concentration (normalized to 18S RNA) in the gastrocnemius muscle of growing animals (3 mo) would be downregulated in a coordinated manner with muscle size during aging-associated atrophy. As indicated by muscle wet weight and total protein content, the gastrocnemius muscle was growing in the 3-mo group (P < 0.01 smaller compared with 12 mo), fully developed at 12 mo, and was atrophied at 24 mo of age (P < 0.05 compared with 12 mo). IGF-I mRNA concentration in the gastrocnemius of 12- and 24-mo-old rats was 39-49% less than in 3-mo-old rats (P < 0.05). Contrary to our hypothesis, there was not a significant skeletal muscle IGF-I mRNA difference between middle age (12 mo) and senescence (24 mo). Thus IGF-I mRNA changed during maturation (3-12 mo) but not during aging (12-24 mo). Skeletal muscle IGF-II mRNA concentration was not different among 3-, 12-, and 24-mo-old animals. Furthermore, animal age did not have an effect on IGFBP-5 mRNA concentration. We conclude that the aging-associated atrophy of skeletal muscle is not caused by altered pretranslational regulation of IGF-I, IGF-II, or IGFBP-5 in skeletal muscle.
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PMID:No effect of aging on skeletal muscle insulin-like growth factor mRNAs. 750 9

Oestradiol is important in the growth of uterine leiomyomata and may act primarily or secondarily through mediators such as growth factors, including the insulin-like growth factors (IGF-I and IGF-II), mitogenic peptides. IGF binding proteins (IGFBPs) modulate IGF actions at their target cells. The objective of this study was to examine the possible steroid dependence of IGF, IGFBP and IGF receptor gene expression and IGFBP synthesis in uterine leiomyomata, using tissues from women cycling normally and made hypo-oestrogenic by a gonadtrophin-releasing hormone agonist (GnRHa). Using a solution hybridization ribonuclease protection assay, anti-sense RNA probes for IGF-I, IGF-II and beta-actin (control) were hybridized with total RNA isolated from leiomyomata exposed in vivo to a range of serum oestradiol (< 40-240 pg/ml) and progesterone (0-10 ng/ml) concentrations. IGF-I gene expression was most abundant in leiomyomata obtained during the late proliferative phase of the cycle and was undetectable in leiomyomata from hypo-oestrogenic patients. IGF-II gene expression was not dependent on endogenous steroid concentrations or cycle stage. IGFBP gene expression was investigated by Northern blotting. The order of relative abundance of IGFBP mRNAs was IGFBP-4 >>> IGFBP-3 >> IGFBP-5 > IGFBP-2 and was not dependent on the in-vivo oestrogen status. Type I and type II IGF receptor gene expression was investigated by polymerase chain reaction using gene-specific primers. Type I and type II IGF receptor mRNAs were detected in leiomyomata and were not dependent on cycle stage or in-vivo oestrogen status. Explant cultures of leiomyomata and myometrium synthesized IGFBP-3 (mol. wt = 38-43 kDa), IGFBP-4, and binding proteins of mol. wt = 34 and 31 kDa. Identification of IGFBP-2 was inconclusive, and IGFBP-1 was not detected. These data support the hypothesis that IGF-I, but not IGF-II, may be a mediator of oestradiol action in the growth of uterine leiomyomata, and that IGFBPs may further modulate, by an autocrine or paracrine mechanism, IGF-I action in this tissue.
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PMID:Insulin-like growth factor (IGF), IGF binding protein (IGFBP), and IGF receptor gene expression and IGFBP synthesis in human uterine leiomyomata. 750 28

We have studied the physiology and tissue expression of IGF-I and IGF-BP3 in pregnant and lactating rats. Specific assays (radioimmunoassays and a binding protein assay) were used to measure serum IGF-I, IGF-II, and IGF-BP levels. IGF-I and IGF-BP3 expression levels were determined in mammary gland and liver by slot-blotting. A sensitive and IGF-I-specific ribonuclease (RNAse) protection assay was further used to detect RNAs transcribed from the IGF-I gene. In the first half of pregnancy, the maternal serum IGF-I concentration rises while the IGF-BP level decreases. This may modify IGF-I availability, thus promoting rapid tissue growth and differentiation. In the second half of pregnancy, the mean serum IGF-I concentration falls sharply from 1140 +/- 150 ng/ml at seven days of pregnancy to 470 +/- 85 ng/ml at 20 days. Post-partum, serum IGF-I increases back to the level obtained in non-pregnant controls within 5 days. Serum levels of IGF-BP, during the same two periods, follow a similar pattern, decrease during pregnancy and increase after parturition. No IGF-II was detected at any time. From the onset of pregnancy to term, IGF-I gene expression in the mammary gland diminishes. In the liver, on the other hand, expression increases during very early pregnancy and diminishes thereafter, remaining below the level measured in non-pregnant animals from mid-pregnancy to term. The pattern of IGF-BP3 expression followed was similar in both organs, with a decrease during gestation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunolocalization and expression of insulin-like growth factor I (IGF-I) in the mammary gland during rat gestation and lactation. 751 39

Insulin-like growth factors (IGFs) have numerous actions on neuronal and glial cell function in vitro, although their in vivo roles within the central nervous system (CNS) remain undefined. Levels of IGF-II are high in most rat tissues before the third postnatal week, but rapidly decrease thereafter, except in the brain and spinal cord, where elevated titers are present in the adult. This suggests a function of IGF-II within the CNS. IGF-binding proteins (IGFBPs) modify the type 1 IGF receptor-mediated activity of IGFs, thereby regulating the activities of IGF-II in the CNS. In this study, we use a ribonuclease protection assay, in situ hybridization, and immunohistochemistry to demonstrate that IGF-II and one of the major CNS binding proteins, IGFBP-2, show a striking congruency in their anatomical pattern of expression and localization throughout the adult rat brain. Both proteins are synthesized predominantly in the leptomeninges, choroid plexus, and parenchymal microvasculature, but become localized, remote from the site of synthesis, in the myelin sheaths of individual myelinated axons and in all of the myelinated nerve tracts in the brain, which presumably represents the site of IGF-II bioactivity. The spatial disparity between sites of synthesis and sites of bioactivity suggests a key role for IGFBP-2 in the regulation of IGF-II bioavailability within the brain.
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PMID:Coordinated pattern of expression and localization of insulin-like growth factor-II (IGF-II) and IGF-binding protein-2 in the adult rat brain. 752 64

GH exerts its biological actions on osteoblasts through a specific high affinity receptor expressed on these cells. GH receptor binding is positively modulated by a number of factors, including retinoic acid and dexamethasone, whereas fetal calf serum strongly decreases the binding. To identify responsible factors in serum, components of serum, the insulin-like growth factors (IGFs)-I and -II, and IGF binding proteins (IGFBPs)-2 and -3 were tested for a possible negative modulatory role. IGF-I and -II decreased [125I]hGH binding at an optimal concentration of 30 ng/ml for IGF-I and 100 ng/ml IGF-II, reducing the binding to 51% and 55%, respectively, of control values. A stimulation of [125I]hGH binding was observed with IGFBP-2 as well as IGFBP-3, inducing an increase to 148% and 151% of control binding at an optimal concentration of 3000 ng/ml for both peptides. The effects of all peptides were dependent on the incubation time, being significantly increased after 8 h of incubation and reaching the full effect thereafter. The effects were declined at 24 h compared with 16 h for IGFBP-2 and -3 but not for IGF-I and -II. Coincubation of the cells with IGF-I and -II and IGFBP-2 and -3 neutralized the effects of the factors alone. In conclusion, these results show that IGF-I and -II on the one hand and IGFBP-2 and -3 on the other hand exert opposite actions on [125I]hGH binding, IGFBP-2 and -3 exerting probably an IGF-independent effect. Further, IGF-I and -II decreased GH receptor messenger RNA (mRNA) levels, as quantified by a solution hybridization ribonuclease protection assay, from 8.65 +/- 1.78 attomoles (amol)/microgram DNA (control) to 2.4 +/- 0.68 and 2.16 +/- 0.92 amol/microgram DNA, respectively. IGFBP-2 increased GH receptor mRNA levels from 5.26 +/- 1.17 (control) to 13.19 +/- 3.48. Incubation with IGFBP-3 did not result in stimulation of GH receptor mRNA levels (8.59 +/- 2.91 amol/microgram DNA). This shows that the mechanism of regulation of the GH receptor is, except for IGFBP-3, at least in part on the mRNA level. Lastly, IGFBP-2 and IGFBP-3 are mitogenic for UMR-106.01 rat osteosarcoma cells, inducing an increase in cell number to 125% and 142% of control cell counts after 48 h of incubation with 1000 ng/ml IGFBP-2 and -3, whereas IGF-I, IGF-II and Long R3 IGF-I did not stimulate proliferation. IGFBP-2 and -3 potentiate hGH induced mitogenesis at low hGH concentrations of both factors, whereas at higher concentrations no such effect is observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Insulin-like growth factor binding proteins-2 and -3 stimulate growth hormone receptor binding and mitogenesis in rat osteosarcoma cells. 754 1

To determine whether tissue production of the IGFs is altered when fetal growth is retarded, IGF-I and -II mRNAs were measured in tissues of fetal sheep subjected to placental restriction and the relationships between IGF gene expression, circulating IGF protein and fetal growth were examined. The majority of potential placental attachment sites were surgically removed from the uterus of 12 non-pregnant ewes to restrict placental size in a subsequent pregnancy. Blood and tissues were collected at 121 days of gestation (term = 150) in 12 fetuses with restricted placental size and eight normal fetuses. IGF-I and IGF-II mRNA was detected by solution hybridization/ribonuclease protection assay in placenta and all fetal tissues studied. IGF-I mRNA was most abundant in skeletal muscle and liver and IGF-II mRNA was highest in kidney and lung. Restriction of placental size reduced fetal weight by 17% and reduced the pO2 (18%) and glucose concentration (23%) of fetal blood. Placental restriction also reduced IGF-I mRNA in fetal muscle (P < 0.002), lung (P < 0.05) and kidney (P < 0.01) but had no significant effect on IGF-II mRNA in any tissue. IGF-I mRNA in fetal liver, kidney and skeletal muscle correlated positively with the concentration of IGF-I protein in fetal blood (P < 0.01). There was no relationship between the concentration of IGF-II protein in fetal blood and IGF-II mRNA in any fetal tissue examined. The concentration of IGF-binding protein-3 (IGFBP-3) in fetal arterial blood plasma measured by RIA correlated positively with fetal weight and with plasma IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of restriction of placental growth on expression of IGFs in fetal sheep: relationship to fetal growth, circulating IGFs and binding proteins. 756 17

Insulin-like growth factors I (IGF-I) and II (IGF-II) are anabolic for osteoblastic cells. Although expression of IGF-I and IGF-II mRNA has been demonstrated in rodent osteoblastic cells, little is known about IGF gene expression in human osteoblastic cell models. In this study we characterized IGF-I and -II mRNA expression in (1) normal human osteoblast-like (hOB) cells, (2) a simian virus 40 immortalized hOB (HOBIT) cell line, and (3) human osteosarcoma cell lines SaOS-2, TE-85, MG-63, and U-2. Since cross-hybridization of IGF cDNA probes with ribosomal RNA obscures detection of some of the multiple IGF transcripts in human cells, we replaced Northern analysis with the more specific ribonuclease protection assay (RPA). We also used the reverse transcriptase-polymerase chain reaction (RT-PCR) to assess whether mRNAs were present at trace levels. IGF-I mRNA expression was consistently observed in normal hOB cells only and by both RT-PCR and RPA. Among IGF-I transcript variants, Ea IGF-I mRNA was more abundant than the Eb mRNA in normal hOB cells. Trace levels of IGF-I mRNA were variably detected in SaOS-2 and U-2 osteosarcoma cells when RT-PCR was performed, but we found no IGF-I mRNA in HOBIT, TE-85, or MG-63 cells. IGF-II mRNA was expressed in normal hOB, HOBIT, TE-85, and U-2 cells as assessed by either method.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Normal human osteoblast-like cells consistently express genes for insulin-like growth factors I and II but transformed human osteoblast cell lines do not. 763 14


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