Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we investigated the involvement of several different pituitary hormones on rat prostate development. 22-day-old Wistar rats, hypophysectomized (hypox) at 19 days of age were supplemented with highly purified human prolactin (hPRL), human luteinizing hormone (hLH), porcine follicle-stimulating hormone (pFSH), and bovine growth hormone (bGH) or with saline. Quantitative analysis of RNAs shows that treatment with either PRL or GH increases significantly steady-state mRNAs levels of the following genes in the prostate: androgen receptor (AR) (respectively 3.5- and 4.8-fold above hypox controls), IGF-I (5- and 2.7-fold), and IGF-I receptor (2.9- and 2.3-fold). LH and FSH, by contrast, have negative effects on these parameters. To test whether the enhancing effect of PRL and GH on AR-mRNA abundance was followed by increased content in the protein itself, binding assays were performed with the androgen agonist [3H]R1881 (131 and 153 fmol/mg protein while hypox controls contained 110 fmol/mg protein). In addition to the well-documented presence of prolactin receptors in prostatic tissues, we have further demonstrated, by means of nuclease S1 protection assays plus dot- and Northern-blot analyses, that a GH receptor mRNA is produced in the immature rat prostate. Moreover, we observed not only strong lactogenic but also purely somatogenic binding to be occurring in the immature prostates. Finally, we have studied IGF-I mRNA content in separated epithelial/stromal cell fractions and have concluded that IGF-I expression is principally located in the prostatic stroma. Taken together, these results suggest that PRL and GH are involved in regulating AR synthesis, at least partially by direct action on the organ. In this context IGF-I appears as a paracrine factor playing a role in epithelium/stroma interactions during prostatic development.
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PMID:Growth hormone and prolactin stimulate androgen receptor, insulin-like growth factor-I (IGF-I) and IGF-I receptor levels in the prostate of immature rats. 136 Sep 28

Insulin-like growth factor-binding protein-3 (IGFBP-3) is the most abundant IGFBP in rat and human sera. The present study demonstrates the expression of the rat IGFBP-3 gene in a large number of tissues and coexpression, but not necessarily equal expression, with IGF-I mRNA. Tissues with a major abundance of IGFBP-3 were kidney, antrum of stomach, placenta, uterus, and liver. Changes in hepatic and renal levels of IGFBP-3 mRNA were analyzed after hypophysectomy (with and without GH treatment) and in the developing postnatal rat. These results were compared to changes in IGF-I mRNA levels under the same physiological conditions. Using S1 nuclease analysis, IGFBP-3 mRNA was present in the kidney and liver of 1-day-old rats and rose significantly in both organs by week 1. Thereafter, levels remained relatively constant, particularly in the liver. This is in marked contrast to the hepatic IGF-I pattern, which showed a continual rise up to 8 weeks. Hepatic IGFBP-3 gene expression was partially GH dependent, with IGFBP-3 mRNA levels falling (approximately 50%) after hypophysectomy and rising slightly after GH treatment. These changes were much less dramatic than those in IGF-I mRNA. In contrast, the renal levels of IGFBP-3 mRNA increased after hypophysectomy, (approximately 100%), but did not decrease with GH treatment. These data suggest that IGFBP-3 mRNA abundance is regulated differently in different tissues, and in at least some tissues is less sensitive to regulation than is IGF-I mRNA.
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PMID:Tissue distribution and regulation of insulin-like growth factor (IGF)-binding protein-3 messenger ribonucleic acid (mRNA) in the rat: comparison with IGF-I mRNA expression. 137 Jan 53

The expression of the insulin-like growth factors (IGFs) and their receptors has been linked to cellular proliferation and tumorigenicity in a number of model systems. Since rhabdomyosarcoma cells express IGF-I receptors, an autocrine or paracrine loop involving this receptor and its ligands could be responsible in part for the growth characteristics of this tumor. To assess directly the role of the IGF-I receptor in rhabdomyosarcoma cell growth and tumorigenicity, a human alveolar rhabdomyosarcoma cell line with high IGF-I receptor expression was transfected with an amplifiable IGF-I receptor antisense expression vector. Four unique, transfected clones were analyzed and found to have reduced IGF-I receptor expression relative to the parental line. Integration of the antisense sequence was demonstrated by Southern blot analysis, and expression of antisense message in these clones was shown by S1 nuclease protection assay. Reduced IGF-I receptor surface expression in the transfectants was shown by decreased immunofluorescence with an IGF-I receptor monoclonal antibody and by decreased IGF-I binding as measured by Scatchard analysis. These clones had markedly reduced growth rates in vitro, impaired colony formation in soft agar, and failed to form tumors in immunodeficient mice when compared with vector-transfected clones. These results demonstrate that reduction of IGF-I receptor expression can inhibit both the in vitro and in vivo growth of a human rhabdomyosarcoma cell line and suggest a role for the IGF-I receptor in mediating neoplastic growth in this mesenchymally derived tumor.
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PMID:Antisense-mediated reduction in insulin-like growth factor-I receptor expression suppresses the malignant phenotype of a human alveolar rhabdomyosarcoma. 808 65

Aims-To determine the role of insulin-like growth factors (IGF) in the proliferation of tumour cells, by studying the mitogenic response to IGFs of three cell lines of differing phenotype established from both malignant rhabdoid and Wilms tumour, representing a range of cell types (GOS 4, G401, and T3/73).Methods-Production of IGF-II and IGF-I was measured by radioimmunoassay, and the presence of IGF binding protein complexes was observed by gel exclusion chromatography. Following growth analyses in serum-free media to ascertain the dependence of the cell lines on exogenous IGFs, the generation of autocrine growth was measured by a density dependence assay of proliferation in culture. Receptors were measured by radioligand cross linking and autocrine growth through these receptors assayed by the use of blocking antibodies.Results-While GOS 4 and G401 were able to proliferate in serum-free medium over a period of 5 d, T3/73 showed an absolute dependence on IGFs added daily at 1-10 ng/ml. Plating at clonal density showed that cell growth was directly density dependent in serum-free medium. The serum independent proliferation of G401 and GOS 4 was blocked by the addition of an antibody to the type 1 IGF receptor (alpha-IR3) suggesting that the effects of autocrine factors are mediated through type 1 IGF receptors. S1 nuclease protection analysis indicated that all three cell lines produced significant amounts of mRNA derived mainly from the P3 IGF-II promoter, but transcripts for IGF-I were undetectable. Radioimmunoassay of IGFs from conditioned media showed that all the lines made assayable IGF-II (8.6, 8.4, and 6.1 ng/ml/24 h/10(6) cells for GOS 4, G401, and T3/73 respectively). The presence of species consistent with both type 1 and type II IGF receptors was demonstrated using radioligand binding to cell membranes followed by cross linking.Conclusions-Autocrine IGF-II may contribute to the serum independence of GOS 4 and G401 cells, whereas T3/73 may depend on exogenous IGF-II for proliferation.
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PMID:IGF-II dependent autocrine growth in cell lines derived from renal tumours of childhood. 1669 34