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Insulin-like growth...
Insulin-like growth factor binding proteins-2 and -3 stimulate growth hormone receptor binding and mitogenesis in rat osteosarcoma cells.
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Slootweg, M C (författare)
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- Ohlsson, Claes, 1965 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine
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Salles, J P (författare)
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visa fler...
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de Vries, C P (författare)
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Netelenbos, J C (författare)
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visa färre...
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(creator_code:org_t)
- 1995
- 1995
- Engelska.
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Ingår i: Endocrinology. - 0013-7227. ; 136:10, s. 4210-7
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- 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)
Nyckelord
- Animals
- Carrier Proteins
- pharmacology
- Cell Division
- drug effects
- Dose-Response Relationship
- Drug
- Growth Hormone
- metabolism
- Insulin-Like Growth Factor Binding Protein 2
- Insulin-Like Growth Factor Binding Proteins
- Insulin-Like Growth Factor I
- pharmacology
- Insulin-Like Growth Factor II
- pharmacology
- Osteosarcoma
- metabolism
- RNA
- Messenger
- analysis
- Rats
- Receptors
- Somatotropin
- genetics
- metabolism
- Time Factors
- Tumor Cells
- Cultured
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- ref (ämneskategori)
- art (ämneskategori)
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