Evidence that IGF-I acts as an autocrine/paracrine growth factor in the magnocellular neurosecretory system: Neuronal synthesis and induction of axonal sprouting

The ability of mature oxytocinergic (OT) and vasopressinergic (VP) neurons of the magnocellular neurosecretory system (MNS) to undergo axonal growth i mplies that one or more growth factors may be active in the adult MNS, yet Little is known regarding their possible identity. One such potential facto r is insulin-like growth factor I (IGF-I). We have examined the expression of IGF-I mRNA and IGF-I-immunoreactivity (IGF-I-ir) in the mature MNS and h ave also determined the in vivo response of OT and VP neurons to hypothalam ic implants of IGF-I. In situ hybridization revealed moderate labeling of I GF-I mRNA in both the supraoptic (SON) and the paraventricular (PVN) nuclei of adult male rats, RT-PCR analysis confirmed the presence of authentic IG F-I mRNA in extracts of the basal hypothalamus, Faint IGF-I-ir was detected in scattered magnocellular neurons within both the PVN and the SON of norm al rats, but IGF-I-ir was much more intense and the majority of MNS neurons including those in the accessory nuclei were immunoreactive in sections fr om rats given colchicine, as were some parvocellular neurons in the PVN. Co nfocal microscopy revealed that IGF-I-ir was present in both OT and VP neur ons, but VP neurons contained the most intense IGF-I-ir. Finally, a dramati c growth response of OT but not of VP fibers was observed following implant ation of polymer rods containing IGF-I into the hypothalamus, A dense OT fi ber plexus grew along the cannula track and OT fibers invaded the leptomeni nges ventral to the SON and encircled the rostral cerebral artery. To our k nowledge this is the first demonstration of axonal sprouting by mature OT n eurons in response to an identified growth factor and the first direct demo nstration of sprouting in response to exogenous IGF-I in the adult CNS, The se findings suggest that IGF-I is synthesized and transported by adult MNS neurons where it may act as an autocrine and/or paracrine growth factor. (C ) 1999 Academic Press.