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Growth Hormone Action on Proliferation and Differentiation of Cerebral Cortical Cells from Fetal Rat

Servicio de Endocrinología (R.A., F.S.-F.), Hospital Carlos III-C.I.C., Instituto de Salud Carlos III, Madrid 28029, Spain; and Servicio de Endocrinología (L.C., C.N.), Hospital Ramón y Cajal, Madrid 28034, Spain

Address all correspondence and requests for reprints to: Dr. Franco Sánchez-Franco, Hospital Carlos III. C/Sinesio Delgado, 10-12, Madrid 28029. E-mail: fsanchez{at}hciii.insalud.es.

To define the role of GH during central nervous system development, we performed studies in cultured rat cerebral cortical cells from 14- (E14) and 17-d-old embryos (E17). The expression of GH receptor, IGF-I receptor, and IGF-I mRNAs was confirmed. In E17, GH increased total cell number (3.9-fold), [³H]-thymidine incorporation (3.5-fold), proliferating cell nuclear antigen levels (2.5-fold), and bromodeoxyuridine (BrdU)-positive cells (2.5-fold). GH action on nestin/BrdUpositive cells was increased in E14 cells at 3 d in vitro (80-fold) but not at 7 d in vitro. In E14 cells, GH increased (9.5-fold) ß-tubulin/BrdU cells. In E17 cells, GH induced neuronal differentiation, as indicated by the absence of ß-tubulin/BrdU-positive cells and the 5.9-fold increment of ß-tubulin protein, and increased glial fibrillary acidic protein/BrdU-positive cells (2.5-fold) and glial fibrillary acidic protein expression (4.5-fold). GH-induced proliferation and differentiation was blocked by IGF-I antiserum. GH increased IGF-binding protein-3 (IGFBP-3), IGF-I receptor protein and its phosphorylation. This study shows that GH promotes proliferation of neural precursors, neurogenesis, and gliogenesis during brain development. These responses are mediated by locally produced IGF-I. GH-induced IGFBP-3 may also have a role in these responses. Therefore, GH is able to activate the IGF-I/IGFBP-3 system in these cerebral cells and induce a physiological action of IGF-I.

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