title: Growth hormone action on proliferation and differentiation of cerebral cortical cells from fetal rat.
abstract: 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), [(3)H]-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/BrdU-positive 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) beta-tubulin/BrdU cells. In E17 cells, GH induced neuronal differentiation, as indicated by the absence of beta-tubulin/BrdU-positive cells and the 5.9-fold increment of beta-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.
authors.affiliation: Servicio de Endocrinología, Hospital Carlos III-C.I.C., Instituto de Salud Carlos III, Madrid 28029, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ajo
authors.forename: Lucinda
authors.initials: L
authors.lastname: Cacicedo
authors.forename: Constanza
authors.initials: C
authors.lastname: Navarro
authors.forename: Franco
authors.initials: F
authors.lastname: Sánchez-Franco
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology* / Q000196:embryology*; D005260:Female; D015870:Gene Expression; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D013006:Growth Hormone / Q000494:pharmacology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D009474:Neurons / Q000166:cytology; D010766:Phosphorylation; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics; D014404:Tubulin / Q000032:analysis
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D014404:Tubulin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1