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:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of hypophysectomy and hormonal replacement therapy on GH receptor (GH-R) gene expression was studied in rat adipose tissue with a cRNA probe corresponding to the amino-terminal of the hepatic GH-R. Male Sprague-Dawley rats, 50-65 days of age, were used. In all fat depots tested (epididymal, retroperitoneal, and sc), two transcripts with an estimated size of 4.0 and 1.2 kilobases (kb), respectively, were detected. An intermediate-size transcript (2.6 kb) was sometimes observed. Also, isolated adipocytes and adipocyte precursor cells from the epididymal fat pad expressed these GH-R transcripts. The pituitary dependance of GH-R gene expression was analyzed in epididymal fat. Hypophysectomies were performed at 50 days of age, and the rats were then given replacement therapy with L-T4 (10 micrograms/kg.day) and hydrocortisone (400 micrograms/kg.day). Hypophysectomy decreased the abundance of both the 4.0 and the 1.2-kb transcripts, an effect that in part was restored by GH treatment. A solution hybridization RNase protection assay was then used to further characterize the effect of GH treatment of hypophysectomized rats on GH-R gene expression. A single injection of human GH (100 micrograms/rat) increased GH-R mRNA levels within 1 h, and maximal levels were reached between 3-12 h after the injection. The increase in GH-R mRNA levels was dose dependent and was observed also after prolonged treatment (1 or 5 mg/kg.day for 6 days) with bovine GH. These results confirm that GH-R mRNAs are present in rat adipose tissue from different fat depots. GH-R transcripts of the same estimated size were detected in isolated adipocytes and adipocyte precursor cells. Furthermore, the results show that there is a rapid and GH-dependent regulation of GH-R mRNA levels in adipose tissue.
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PMID:Expression and regulation of growth hormone (GH) receptor messenger ribonucleic acid (mRNA) in rat adipose tissue, adipocytes, and adipocyte precursor cells: GH regulation of GH receptor mRNA. 171 28

We have investigated the effect of growth hormone (GH) treatment on GH receptor mRNA expression in five prepubertal children with Prader-Willi syndrome and in eight patients with GH deficiency. An adipose tissue needle biopsy was taken before and after 2-4 mo of GH treatment, and RNA was isolated from adipose tissue and from adipocytes. GH receptor mRNA levels were determined by an RNase protection/solution hybridization assay. To further assess the specificity of the assay for GH receptor mRNAs, RNA extracted from human adipose tissue was subjected to Northern blot analysis. GH treatment significantly increased GH receptor mRNA levels in adipose tissue and isolated adipocytes. Our results indicate that GH may have an important role in regulating the GH receptor in humans.
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PMID:Growth hormone (GH) treatment up-regulates GH receptor mRNA levels in adipocytes from patients with GH deficiency and Prader-Willi syndrome. 749 69

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

The growth hormone (GH) receptor is essential for the actions of GH on postnatal growth and metabolism. To identify DNA sequences involved in the regulation of transcription of the murine GH receptor gene, a 17-kilobase genomic clone containing the 5'-flanking region, exon 1, and part of intron 1 of the murine GH receptor gene was isolated. Utilizing primer extension and ribonuclease protection assays, two major transcription start sites were identified in RNA from liver of male, female, and pregnant mice. Transient transfection studies using a reporter gene demonstrated promoter activity in a variety of eukaryotic cells. Deletional analysis and DNA-protein binding assays led to the identification of a 30-base pair enhancer element located about 3.4 kilobases upstream of the transcription start sites. Computer analysis of the nucleotide sequence of the enhancer element did not reveal any potential DNA binding motifs for known transcription factors, and this DNA element failed to exhibit binding activity for some common transcription factors. Analysis of both functional activity and DNA-protein binding activity of this enhancer element in adult and fetal hepatocytes suggests that this DNA element may play a role in the developmental expression of the GH receptor gene.
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PMID:Cloning of the promoter-regulatory region of the murine growth hormone receptor gene. Identification of a developmentally regulated enhancer element. 772 93

Multiple alternatively spliced 5' untranslated regions (5'UTRs) have been identified in growth hormone (GH) receptor mRNA isolated from hepatic and adipocyte tissue. In the present study, the preferential utilisation of a GC-rich 5'UTR, designated exon 1B, was observed following the isolation of ovine (o) GH receptor cDNA clones from a skeletal muscle cDNA library. Although exon 1B-oGH receptor mRNA was expressed in all tissues examined, marked differences in the level of expression relative to the whole GH receptor transcript pool were observed between tissues. A single genomic clone (lambda 9) was isolated that encompassed exon 1B, together with 6 kilobase pairs of 5' and 12 kilobase pairs of 3' flanking sequence. Multiple transcription initiation sites were identified using RNase protection analysis on skeletal muscle poly(A)+ RNA, a result consistent with the absence of a proximal TATA box element. A CAAT box (-37 to -33) and a putative binding site for SP1 (a GC box -68 to -63) were found in the sense orientation immediately upstream of major transcription initiation site. Transfection of a series of overlapping promoter fragments linked to the luciferase reporter gene into HuH7, CHO and HeLa cells defined a core promoter element of 134 base pairs that was sufficient for maximum promoter activity. The emerging complexity of the 5' regulatory region of the GH receptor gene was emphasised by the observation that probes derived from exon 1B and the distal 3' intron boundary do not hybridise with previously cloned genomic sequences that span the liver-specific P1 promoter and exon 2.
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PMID:Differential expression of growth hormone receptor messenger RNA from a second promoter. 775 37

In the rat, the GH receptor (GHR) and the GH-binding protein (GHBP), which arise from alternative splicing of the same gene, show a sexually dimorphic and GH-dependent expression pattern. Multiple alternative 5'-untranslated regions (UTRs) are present in GHR and GHBP transcripts in the rat, one of which, GHR1, has recently been shown to be liver specific and found at higher levels in females. We have measured the hepatic GHR1, GHR, and GHBP transcript levels, by RNase protection and solution hybridization assay, in animals with differing hormonal status, in which hepatic GHR binding and plasma GHBP have been previously assayed. Estradiol (E2) induced GHR1 in males, whereas ovariectomy or the antiestrogen tamoxifen reduced GHR1 expression in females. The induction of GHR1 by E2 was GH dependent, being lower in GH-deficient dwarf rats and absent in hypophysectomized rats, paralleling previous measurements of plasma GHBP and hepatic GHR binding in these animals. Significant changes in GHR1 could explain the trends seen in the same extracts when coding region probes were used. Short-term adrenalectomy had no effect on GHR and GHBP expression, but dexamethasone markedly reduced both protein and messenger RNA (mRNA) levels. Corticosterone treatment had no effect alone but reduced the E2-induced increase in GHR1 levels, whereas methylprednisolone administered orally reduced hepatic GH binding, plasma GHBP, and GHR1 mRNA levels. Thus, 5'-UTRs, encoded by different first exons, are involved in the regulation of hepatic GHR and GHBP expression and need to be considered when comparing effects of hormonal manipulation on the mRNA transcripts and protein products of the GHR gene. Previous studies have found discrepancies between levels of protein expression and mRNA transcripts measured only with coding region probes. Our results suggest that posttranscriptional differences related to 5'-UTR heterogeneity in the GHR gene explain some of these discrepancies.
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PMID:Steroid regulation of growth hormone (GH) receptor and GH-binding protein messenger ribonucleic acids in the rat. 782 33

The GH-binding protein (GHBP) in rodents consists of a ligand-binding domain, which is identical to the extracellular portion of the GH receptor (GHR), and a hydrophilic carboxyl-terminal domain, in place of the transmembrane and intracellular domains of the GHR. The two proteins are encoded by separate messenger RNAs (mRNAs), which are believed to be derived from a single gene by alternative splicing. In the present study, we report the gestational profiles of mouse GHR (mGHR) and mGHBP mRNAs in adipose tissue, brain, heart, kidney, liver, lung, mammary gland, muscle, ovary, and pituitary and describe the ontogeny of both messages in the liver of late gestational fetuses and newborns. A ribonuclease protection assay was used to simultaneously detect the two transcripts with an antisense RNA probe complementary to the extracellular domain- and hydrophilic tail-encoding regions of the mRNAs. Levels of hepatic GHR and GHBP mRNAs increased with fetal age. In the maternal liver, the abundance of both messages increased during pregnancy, with GHR mRNA levels rising less than GHBP mRNA. Also, the ratio between the two messages in this tissue increased during pregnancy in favor of mGHBP mRNA. In maternal mammary tissue, however, expression levels of both transcripts decreased gradually throughout pregnancy starting on day 8 of gestation and declining further during lactation, reaching a minimum 7-fold reduction on day 6 of lactation relative to nonpregnant values. Although there were no pregnancy-related changes in the remaining tissues we examined, the ratio of the abundance of GHR mRNA to that of GHBP mRNA varied tissue specifically. In the maternal brain, heart, liver, and mammary gland, mGHBP mRNA levels were higher than mGHR mRNA levels. In the maternal muscle and adipose tissue, the abundance of the two mRNA species was comparable. These observations indicate a gestational, developmental, and tissue-specific regulation of the expression of mGHR and mGHBP species.
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PMID:Expression and distribution of messenger ribonucleic acids for growth hormone (GH) receptor and GH-binding protein in mice during pregnancy. 783 69

We studied the ontogeny of GH receptor mRNA levels and the effect of exogenous estradiol administration on GH receptor mRNA levels in rabbit liver. A solution hybridization-RNase protection assay revealed a predominant 370-base long protected band corresponding to the mRNA encoding the transmembrane GH receptor, and a 241-base long protected band, representing about 9.0%, with the predicted size for the truncated form of the GH receptor. To study the developmental profile of GH receptor expression, we studied 12 female rabbits, at ages 1, 3, 5 and 7 months. Maximal GH receptor mRNA levels were observed in 3-month-old animals and decreased in 7-month-old animals. To investigate the effect of estradiol, 8-week-old immature female rabbits were randomly divided into five groups, and received subcutaneous pellets containing either placebo or estradiol at doses of 0.1, 0.5, 1.5 and 5.0 mg for 3 weeks. Exogenous administration of estradiol, at doses that resulted in physiological circulating levels, induced a reduction in GH receptor expression, measured both by GH binding (36 and 46%), and GH receptor mRNA levels (38 and 87%), in animals receiving pellets containing 1.5 and 5.0 mg of estradiol, respectively. We conclude that estradiol decreases GH receptor expression in rabbit liver. The results of our study suggest that there is an inverse relationship between circulating estrogen concentrations and liver GH receptor expression.
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PMID:Estradiol inhibits growth hormone receptor gene expression in rabbit liver. 795

Abnormalities of GH secretion and clearance are well-documented in poorly controlled insulin-dependent diabetes mellitus (IDDM), but the contribution of the receptor (GHR) and the GH-binding protein (GHBP) to these abnormalities has not been defined. We studied the expression of the GHR/GHBP gene in the livers, hearts and kidneys in streptozocin-induced diabetes (STZ-D) in the rat. GHR and GHBP mRNA levels were measured by Northern blot and ribonuclease protection assays. Whereas levels of GHR and GHBP mRNA were significantly decreased in liver and heart of STZ-D rats when compared with the control group (P < 0.01), GHR mRNA was significantly increased in the kidneys of STZ-D rats (P = 0.03). Six days of insulin treatment did not significantly alter the levels of GHR/GHBP mRNA in the liver or heart of STZ-D rats, but significantly decreased GHBP mRNA (P = 0.04) in the kidney. Circulating IGF-I was reduced, as was IGF-I mRNA in the liver and heart of STZ-D rats; only circulating IGF-I was restored by insulin treatment. Neither STZ-D nor insulin treatment affected IGF-I or IGF-I receptor mRNA concentrations in the kidney. We conclude that (1) STZ-D modulates the expression of the GHR/GHBP gene and (2) that these changes in GHR/GHBP mRNA concentrations are tissue-specific; STZ-D decreases GHR/GHBP mRNA in liver and heart tissue but increases GHR mRNA concentrations in the kidney. Our results indicate a role for decreased numbers of hepatic GHRs in the pathogenesis of resistance to GH's actions in terms of IGF-I generation and promotion of linear growth in IDDM. We postulate that increased GHR expression in the kidney may be involved in the renal complications of IDDM.
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PMID:Tissue-specific regulation of the growth hormone receptor gene in streptozocin-induced diabetes in the rat. 796 96

In uremia, reduced longitudinal growth and decreased hepatic insulin-like growth factor-I (IGF-I) secretion despite elevated GH serum levels point to an insensitivity to the action of GH. The molecular basis that accounts for this insensitivity could comprise decreased GH receptor expression in the target organs for GH or binding of GH in the circulation to substances that compete with the receptor. To address this hypothesis, the abundance of hepatic GH receptor mRNA was measured by solution hybridization RNase protection assay in uremic female Sprague-Dawley rats, following two-stage 5/6 nephrectomy, and in pair-fed and in ad libitum-fed sham-operated controls; rat GH binding protein (GHBP) plasma concentration was measured by a sensitive direct RIA. Uremia was associated with a 50% decrease of hepatic GH receptor expression compared to pair-fed controls, which themselves showed a 25% reduction of hepatic GH receptor mRNA abundance when compared to ad libitum-fed controls. Plasma GHBP levels in uremia were markedly higher than in both control groups. Treatment with recombinant human GH (rhGH) (10 IU/kg body wt per day s.c. for 10 days) led to a comparable induction of IGF-I plasma levels and weight gain in uremia and pair-fed controls, indicating that the insensitivity to GH in uremia can be overcome by large rhGH doses. Subcutaneous rhGH injections did not significantly alter the hepatic GH receptor transcript abundance or plasma GHBP levels in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced hepatic growth hormone (GH) receptor gene expression and increased plasma GH binding protein in experimental uremia. 800 78


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