Estradiol modulates insulin-like growth factor I receptors and binding proteins in neurons from the hypothalamus.
Trophic effects of 17 beta-estradiol (beta E2) on in vitro developing hypothalamic cells have been reported. Insulin-like growth factor I (IGF-I) is also a potent trophic factor for cultured hypothalamic cells. An interaction between sexual steroids and insulin-like growth factors (IGFs) in modulating growth of hypothalamic cells has been suggested. Thus, we tested whether beta E2 modulates the levels of IGF-I, its membrane receptor and its binding proteins in rat hypothalamic cultures. Using both neuron- and glial-enriched cultures obtained from fetal rat hypothalami we found that addition of beta E2 elicited a significant increase in IGF-I receptor levels in neurons, without affecting its affinity. On the other hand, the three different IGF-binding proteins (IGFBPs) found in the conditioned medium of the cultures were differentially modulated by beta E2 in the two types of cells studied. Overall, neuronal cultures produced greater amounts of IGFBPs after treatment with beta E2, with IGFBP2 reaching significantly higher levels. On the contrary, treatment with beta E2 did not significantly alter the amounts of IGFBPs produced by glial cells. Finally, the levels of immunoreactive IGF-I found either in the medium or in cellular extracts in both neuronal and glial cultures were not modified by treatment with beta E2. These results strongly support previous observations of a trophic synergistic interaction between IGFs and beta E2 on hypothalamic cells. Thus, an increase in IGF-I receptors and/or IGFBPs after exposure to beta E2 may result in an enhanced response of hypothalamic neurons to IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
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Laboratory of Cellular and Molecular Neuroendocrinology, Cajal Institute, CSIC, Madrid, Spain.
Torres-Aleman
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D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004958:Estradiol / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D018969:Insulin-Like Growth Factor Binding Proteins; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1