IGF-binding proteins are differentially regulated in an ovarian granulosa cell line

We have recently established an immortalized granulosa cell line as a model system to investigate ovarian function, with particular emphasis on the insulin-like growth factor (IGF) regulatory system. Previous results have shown that these cells express mRNAs for IGF-binding proteins (IGFBPs)-2 to -5. These IGFBPs are also detected by ligand blots. The current work evaluated the regulation by the IGFs and cAMP on the IGFBPs and their mRNAs and compared the findings to that in primary culture. Our results indicate that levels of the IGFBPs are controlled, in part, by expression of the mRNAs. However, evidence for post-transcriptional regulation was also discovered. IGFBP-3 was stimulated by IGF-I, IGFBP-4 by forskolin, and IGFBP-5 by IGF-I. IGFBP-2, -3, and -4 are expressed under basal conditions whereas IGFBP-5 is only detectable after IGF-I induction. An alteration in the biphasic actions of cAMP in this cell line, as compared to primary culture, was evident.