title: Localization of insulin-like growth factor binding protein-2 messenger RNA during postnatal brain development: correlation with insulin-like growth factors I and II.
abstract: Insulin-like growth factor binding protein-2 binds insulin-like growth factors I and II with high affinity and modulates the interaction of these ligands with the type I insulin-like growth factor receptor. Previously we have shown that insulin-like growth factor binding protein-2 and insulin-like growth factor-I gene expression are spatiotemporally co-ordinated in the developing retina and cerebellum. The present study examined other brain regions and found a similar correlation in insulin-like growth factor binding protein-2 and insulin-like growth factor-I gene expression in relay stations of developing sensory and cerebellar networks of the rat. In these sites, as in the cerebellum and retina, insulin-like growth factor-I messenger RNA is localized in the principal or projection neurons and insulin-like growth factor binding protein-2 messenger RNA is localized in surrounding astroglia. Outside these sensory relay centers, the relationship of insulin-like growth factor binding protein-2 to insulin-like growth factor-I gene expression is not so well defined. In the hippocampal formation, insulin-like growth factor-I messenger RNA is present in large interneurons and insulin-like growth factor binding protein-2 messenger RNA in regional astrocytes; their timing is co-ordinated, with peak levels seen about postnatal day 12, but their anatomical association is not apparent. The least degree of correlation between local insulin-like growth factor-I and insulin-like growth factor binding protein-2 gene expression is found in the neocortex, where insulin-like growth factor-I is abundant in scattered large neurons from postnatal days 3 to 20. In contrast, insulin-like growth factor binding protein-2 messenger RNA is widely expressed throughout the neocortex from before birth to about postnatal day 12, in a pattern consistent with expression by nascent astroglia. Insulin-like growth factor binding protein-2 gene expression is greatly reduced throughout the brain by the third week after birth; in response to optic nerve transection, however, there is a resurgence of gene expression for this factor by activated astrocytes in affected retinal target regions. Insulin-like growth factor binding protein-2 and insulin-like growth factor-II messenger RNAs are co-localized in the choroid plexus and leptomeninges from the time of birth onward without diminution. In summary, insulin-like growth factor binding protein-2 demonstrates complex patterns of gene expression during postnatal brain development--some of which appear to be closely related to local insulin-like growth factor synthesis and some of which appear independent of it.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.
authors.forename: W H
authors.initials: WH
authors.lastname: Lee
authors.forename: K M
authors.initials: KM
authors.lastname: Michels
authors.forename: C A
authors.initials: CA
authors.lastname: Bondy
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development*; D001923:Brain Chemistry / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis*; D003714:Denervation; D005260:Female; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II