Regulation of growth-hormone-receptor gene expression by growth hormone and pegvisomant in human mesangial cells
| Autor: | Primus E. Mullis, Amélie Besson, Andrée Eblé, Jean-Daniel Sraer, Udo Meinhardt, Christian J. Strasburger |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Collagen Type IV
mesangial cells medicine.medical_specialty Growth-hormone-releasing hormone receptor medicine.medical_treatment Gene Expression 030209 endocrinology & metabolism Growth hormone receptor Biology Collagen Type I 03 medical and health sciences 0302 clinical medicine Growth hormone-binding protein growth hormone binding protein Internal medicine medicine Humans Insulin-Like Growth Factor I Growth Hormone Receptor Antagonist Cells Cultured 030304 developmental biology 0303 health sciences Mesangial cell Human Growth Hormone Reverse Transcriptase Polymerase Chain Reaction Growth factor Receptors Somatotropin Culture Media Glomerular Mesangium Insulin-Like Growth Factor Binding Protein 1 Endocrinology growth-hormone-receptor Nephrology Hormone receptor growth hormone Pegvisomant transcription medicine.drug |
| Zdroj: | Kidney International. 64:421-430 |
| ISSN: | 0085-2538 |
| DOI: | 10.1046/j.1523-1755.2003.00117.x |
| Popis: | Regulation of growth-hormone-receptor gene expression by growth hormone and pegvisomant in human mesangial cells.BackgroundMice transgenic for growth hormone develop mesangial proliferation, glomerular hypertrophy, and progressive glomerular sclerosis suggesting that the growth hormone–insulin-like growth factor I (IGF-I) pathway plays an important role. Therefore, we studied the impact of variable concentrations of 22 kD, 20 kD growth hormone, as well as of the growth hormone receptor antagonist pegvisomant (B2036-PEG), on both the growth hormone receptor (GHR/GHBP) gene expression and growth hormone binding protein (GHBP) formation in a human glomerular mesangial cell line. Further, the impact on collagen, IGF-I and IGF binding protein-1 (IGFBP-1) formation was studied.MethodsIn order to assess transcription, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used.ResultsPhysiologic doses of 22 kD or 20 kD growth hormone caused a dose-dependent and significant (P < 0.01) up-regulation of GHR/GHBP gene transcription, whereas supraphysiologic doses (50 and 500ng/mL) resulted in down-regulation (P < 0.001). Whenever pegvisomant was used, there was no increase in GHR/GHBP expression. These data were confirmed using run-on experiments. Further, the assessment of GHBP presented a constant, dose-dependent increase, which was completely abolished in the experiments where pegvisomant was used.ConclusionWe present data showing that growth hormone has a direct impact on GHR/GHPB gene transcription and that pegvisomant is a potent growth hormone receptor antagonist in human mesangial cells. In addition, although the GHR/GHBP gene transcription is down-regulated by supraphysiologic growth hormone concentrations, this effect was not found when GHBP levels were measured. This finding may reflect a self-inhibitory effect of growth hormone on the level of GHR/GHBP gene transcription, which does not involve the regulation of the shedding of GHBP and may, therefore, be of physiologic interest. |
| Databáze: | OpenAIRE |
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