[Frontiers in Bioscience 2, d88-125, March 1, 1997]
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CROSS-TALK SIGNALS IN THE CNS: ROLE OF NEUROTROPHIC AND HORMONAL FACTORS, ADHESION MOLECULES AND INTERCELLULAR SIGNALING AGENTS IN LUTEINIZING HORMONE-RELEASING HORMONE (LHRH)-ASTROGLIAL INTERACTIVE NETWORK

Bianca Marchetti

Department of Pharmacology, Medical School, University of Catania, 95125 Catania, Laboratory of Biotech. Neuropharmacology, OASI Institute for Research and Care (IRCCS) on Mental Retardation and Brain Aging (IRCCS) Troina, (EN), Italy.

Received 8/2/96; Accepted 2/20/97; On-line 3/1/97

15. Progression and competent growth factors exert direct neurotrophic and functional effects on the GT1-1 neuronal cell line: presence of synergism/cooperativity

Stiles and coworkers (248) have allowed the classification of mitogens as "competence" or "progression" factors that cooperate for a full mitogenic response. Competence factors are not able to induce DNA synthesis, but give the "competence" to respond to other hormones ("progression factors") that stimulate "progression" through the cell cycle. Incompetent cells do not respond to progression factors and remain arrested. The category of competence factors include platelet derived growth factor (PDGF) and fibroblast growth factor (FGF), while the progression factors include epidermal growth factor (EGF) and the insulin family of growth factors (IGFs). Since diffusible molecules of peptide nature were previously shown to participate in GT1-1 neuron-astroglia crosstalk, the participation of different growth factors (GFs) was tested by: a. assessment of their ability to directly exert, either alone or in combination, neurotrophic effects during GT1-1 neuronal differentiation; b. perturbation experiments aimed at neutralizing a specific GF during GT1-1 neuron-astroglia interactions. Our recent data (44) provide evidence that bFGF, EGF, IGF-I and Ins can directly exert neurotrophic effects and variously influence cell survival/proliferation and GT1 functional capacity. Moreover, a synergism /cooperativity between the competent factor, bFGF, and the progression factors (EGF, Ins and IGF-I) was measured indicating the possibility that the sequential expression of these factors during development may differentially regulate LHRH neuronal migration, differentiation and modulate the ability of these neurons to elaborate and secrete the neuropeptide.

In rodents, neurogenesis is completed before birth, but gliogenesis occurs in the first week of postnatal life, and it is possible that different mitogenic peptide growth factors may be involved in the regulation of the two processes. Both competence and progression factors were found to differentially affect GT1 neurons according to the specific GF, the schedule of administration, and the stage of GT1-1 neuron differentiation (44).