The insulin-like growth factor system in the GT1-7 GnRH neuronal cell line

Evidence suggests that insulin-like growth factors (IGFs; IGF-I and IGF-II) are involved in the regulation of reproductive function including the deve lopment of the gonadotropin-releasing hormone (GnRH) neuronal system and th e modulation of GnRH secretory activities. To further characterize the regu latory role of the IGF system on GnRH neuronal function, we have examined t he gene expression of IGF-I, IGF-II, IGF-I receptor (IGF-IR), and IGF-bindi ng proteins (IGFBPs) in a GnRH neuronal cell line (GT1-7 cells). The relati ve effects of IGFs and insulin on GnRH secretion by these cells was also in vestigated. RT-PCR analysis demonstrated IGF-I, IGF-II and IGF-IR mRNAs in GT1-7 cells. The mRNAs for IGFBP-2, -3, -4, -5 and -6 but not IGFBP-1 were also detected. Immunoreactive protein bands for IGFBP-2, -4 and -5 but not for other IGFBPs were demonstrated by Western blot with IGFBP-5 appearing t o be the most abundant IGFBP secreted by GT1-7 cells. IGFBP-5 production by GT1-7 cells was stimulated by both IGF-I and IGF-II in a dose-dependent ma nner with approximately equal potency, whereas insulin caused no significan t effect. GnRH secretion by GT1-7 cells treated with IGF-I or IGF-II but no t insulin showed an increase (80-100%) at 2 h of treatment followed by a de crease (46%) at 6 h that continued up to 24 h. We conclude that the express ion of IGFs, IGF-IR and IGFBPs and their interactions in the regulation of GnRH secretion by GT1-7 cells as demonstrated by our study provide a basis for an autocrine regulatory role for the IGF system in GnRH neuronal secret ory activities. Copyright (C) 1999 S. Karger AG, Basel.