Abstract
PTH treatment of UMR 106-01 rat osteosarcoma cells increased 20-to 100-fold medium levels of a discrete insulin-like growth factor binding protein (IGFBP) with Mr of 29K. Northern analysis of UMR cellular RNA hybridized with a specific IGFBP-5 complementary DNA probe indicated a 6.0-kilobase transcript induced within 2 h in PTH-treated cells. IGFBP-5 messenger RNA (mRNA) abundance was maxmal around 6 h and remained elevated after 24 h of treatment. Another rat oeteosarcoma cell line (ROS 17/2.8) did not express IGFBP-5 mRNA and did not secrete 29K IGFBP. Induction of IGFBP-5 mRNA by PTH was blocked when RNA synthesis in UMR cells was inhibited by actinomycin D. (Bu)2cAMP mimicked the effect of PTH on IGFBP-5 mRNA expression and protein secretion. In addition, a monoclonal antibody against IGF-I (Sm1.2) inhibited the PTH-induced increase in medium IGFBP-5 without influencing IGFBP-5 transcript levels. Direct addition of IGF-I to UMR cell cultures increased medium IGFBP-5 levels approximately 14-fold, with a modest effect on IGFBP-5 mRNA levels. Studies comparing IGF-I, IGF-II, different IGF-I analogs, and insulin indicated that the predominant IGF effect on IGFBP-5 accumulation was type I IGF receptor independent. Thus, in UMR 106-01 cells, PTH and IGF-I increase extracellular concentrations of IGFBP-5 via distinct but coordinate mechanisms; PTH acts primarily to induce IGFBP-5 mRNA expression through a cAMP-mediated mechanism, and IGF-I appears to interact directly with IGFBP-5 protein to promote its accumulation.
Original language | English (US) |
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Pages (from-to) | 2525-2530 |
Number of pages | 6 |
Journal | Endocrinology |
Volume | 132 |
Issue number | 6 |
State | Published - Jun 1993 |
ASJC Scopus subject areas
- Endocrinology