title: Binding and action of insulin-like growth factor I in pituitary tumor cells.
abstract: Insulin-like growth factor I (IGF-I), a target hormone mediating most of the growth effects of GH, suppresses GH gene expression in a feedback regulatory loop, which may be either endocrine or paracrine in nature. Although IGF-I has been shown to directly attenuate GH gene transcription, the relationship of IGF-I binding and action in the somatotroph cell remains unclear. Therefore, IGF-I binding and action were compared in two different pituitary cell lines both secreting GH. Recombinant human IGF-I attenuated GH secretion in GC cells by up to 70% after 48 h in a dose-dependent manner. Surprisingly, IGF-I failed to suppress GH secretion in GH3 cells, a clonally related pituitary cell line. Binding studies showed that although the KD for IGF-I was similar in both cell types, GC cells contain 3-fold more IGF-I binding sites compared to GH3 cells, possibly explaining their resistance to IGF-I action. Nevertheless, both cell lines possessed abundant and similar binding sites for insulin. These results imply that the IGF-I signal for GH gene regulation is receptor-mediated and directly correlated with the number of pituitary IGF-I binding sites. Availability of pituitary IGF-I binding sites may therefore be important in determining the level of GH expression by the somatotroph.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center-UCLA School of Medicine 90048.
authors.forename: H
authors.initials: H
authors.lastname: Yamasaki
authors.forename: D
authors.initials: D
authors.lastname: Prager
authors.forename: S
authors.initials: S
authors.lastname: Gebremedhin
authors.forename: L
authors.initials: L
authors.lastname: Moise
authors.forename: S
authors.initials: S
authors.lastname: Melmed
mesh_terms: D000818:Animals; D001665:Binding Sites; D013006:Growth Hormone / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D009994:Osmolar Concentration; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone