ABSTRACT
Insulin-like growth factor (IGF)/IGF binding protein (IGFBP) abnormalities may be important in the pathogenesis of growth failure in chronic renal failure (CRF). We induced experimental CRF by 5/6 nephrectomy in Sprague Dawley rats (100 g) and observed for 2 weeks comparing with sham-operated pair-fed control rats (Sham- C). CRF rats gained 30% less height than Sham- C rats (P10 kDa, containing IGFBPs) and low (<10 kDa, containing free IGF) molecular weight fractions using a gel filtration column. Both fractions obtained from CRF sera decreased the growth of control chondrocytes up to 40% compared with those from control sera. We suggest that the pathogenesis of growth failure in CRF may be involved in the increase of circulating IGFBP4 as well as the unidentified small molecular weight uremic serum factors which block the growth of chondrocytes in growth plate.
Subject(s)
Animals , Male , Rats , Cell Proliferation , Cells, Cultured , Chondrocytes/cytology , Insulin-Like Growth Factor Binding Protein 4/analysis , Kidney Failure, Chronic/blood , Liver/chemistry , Muscle, Skeletal/chemistry , RNA, Messenger/analysis , Rats, Sprague-Dawley , Somatomedins/analysisABSTRACT
Gonadotropin releasing hormone agonist(GnRHa) has been used as a temporaruy medical management for uterine myoma. Insulin-like growth factors(IGFs) has been supposed to play an etiological role in myoma growth and their action is modulated by IGF-binding proteins(IGFBPs). The purpose of this study is to evaluate the effects of GnRHGa on the IGFBPs production in the explant culture of adjacent myometrium and uterine myoma. The adjacent myometrium and myoma explants from patients treated(n=10) and nontreated(n=16) with GnRHa were cultured under serum free condition.Some explants from untreated patients were also cultured in the presence of GnRHa(10(-7) M/L). Western ligand blot and immunoprecipitation showed the presence of 276 kilodalton IGFBP, IGFBP-2, IGFBP-3 and IGFBP-4 in culture media of these explants and IGFBP-4 only was consistently present in culture media of all explants. There were no significant differences in the frequency of each IGFBP between adjacent myometrium and myoma explant cultures regardless of the type of GnRHa exposure. The relative IGFBP-4 level in explant cultures of myoma from patients treated with GnRHa was significantly higher than that from untreated patients.Addition of GnrHa in the media of myoma explants did not result in an significant change in the relative IGFBP-4 level compared with in vitro untreated explant cultures. Our data suggest that Gnrha may act through indirect involvement in the EGFBP-4 production in myoma tissue.
Subject(s)
Animals , Female , Humans , Mice , Culture Media , Gonadotropin-Releasing Hormone , Gonadotropins , Immunoprecipitation , Insulin-Like Growth Factor Binding Protein 2 , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor Binding Protein 4 , Insulin-Like Growth Factor Binding Proteins , Leiomyoma , Myoma , MyometriumABSTRACT
Gonadotropin releasing hormone agonist(GnRHa) has been used as a temporaruy medical management for uterine myoma. Insulin-like growth factors(IGFs) has been supposed to play an etiological role in myoma growth and their action is modulated by IGF-binding proteins(IGFBPs). The purpose of this study is to evaluate the effects of GnRHGa on the IGFBPs production in the explant culture of adjacent myometrium and uterine myoma. The adjacent myometrium and myoma explants from patients treated(n=10) and nontreated(n=16) with GnRHa were cultured under serum free condition.Some explants from untreated patients were also cultured in the presence of GnRHa(10(-7) M/L). Western ligand blot and immunoprecipitation showed the presence of 276 kilodalton IGFBP, IGFBP-2, IGFBP-3 and IGFBP-4 in culture media of these explants and IGFBP-4 only was consistently present in culture media of all explants. There were no significant differences in the frequency of each IGFBP between adjacent myometrium and myoma explant cultures regardless of the type of GnRHa exposure. The relative IGFBP-4 level in explant cultures of myoma from patients treated with GnRHa was significantly higher than that from untreated patients.Addition of GnrHa in the media of myoma explants did not result in an significant change in the relative IGFBP-4 level compared with in vitro untreated explant cultures. Our data suggest that Gnrha may act through indirect involvement in the EGFBP-4 production in myoma tissue.