Autocrine Role of Insulin‐like Growth Factor II Secretion by the Rat Choroid Plexus

Abstract

Insulin-like growth factor II (IGF-II) is expressed and secreted by the choroid plexus and has been suggested to act as a trophic factor in the adult mammalian central nervous system. The aim of the present study was to investigate whether IGF-II has an autocrine role in the choroid plexus. Using in situ hybridization we demonstrate that IGF-II is primarily expressed in the epithelium of adult rat choroid plexus. Conditioned medium from primary cultures of purified rat choroid plexus epithelial cells, intact choroid plexus tissue, as well as rat CSF, displaced IGF-II binding to a 23 HMM melanoma cell line in an IGF-II radioreceptor assay. The presence of IGF-II and IGF binding protein-2 in conditioned medium was shown by Western immunoblot. The mitotic activity in choroid plexus epithelial cell cultures was quantified by immunohistochemical staining of bromodeoxyuridine incorporated into cell nuclei. A monoclonal antibody towards IGF-II inhibited cell division by 35%, while IGF-I increased the number of stained nuclei by 75%. Basic fibroblast growth factor stimulated cell division at low concentrations, but had no effect at high concentrations. Growth hormone had no effect. We conclude that IGF-II in the choroid plexus could have an autocrine role in the regulation of choroid plexus epithelial cell growth.

Expression of a novel member of the TGF-β superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues

“…Secretion of GDF-15/MIC-1 into the CSF probably permits the protein to enter the brain parenchyma, where it may act as a neurotrophic factor (J. Strelau, personal communication). Similar routes of action and effects have been described for insulin-like growth factor II (IGF-II), which is also produced and secreted by the choroid plexus and has been suggested to act as a trophic factor in the adult mammalian nervous system (see Ishii 1993 for a review; Nilsson et al 1996).…”

Expression of Insulin-Like Growth Factor Binding Protein-2 during Postnatal Development of the Rat Neurointermediate Pituitary

“…It is noteworthy that the intensity of hybridization signal is consistently greater over mature pituicytes than it is over cells of the choroid plexus which presumably secrete IGFBP-2 into the cere brospinal fluid [40,43] (compare fig. 3 and 5).…”

Insulin-like growth factor-1 and insulin-like growth factor binding proteins in cerebrospinal fluid during the development of mouse embryos

“…9 IGF is secreted by the choroid plexus. 10 IGF in the CSF can pass through the ependymal layer and reach the brain parenchyma. 11 Choroid plexus-derived IGF might be important for cellular survival and recovery shortly after injury, before neural tissue starts to produce its own growth factors.…”