title: Reduced pericellular sensitivity to IGF-I in fibroblasts from girls with Turner syndrome: a mechanism to impair clinical responses to GH.
abstract: Girls with Turner syndrome (TS) are treated with supraphysiological doses of growth hormone (GH) to improve final height; however in some girls, the growth response can be poor. This may reflect aberrations in GH and/or IGF-I actions at the cellular level, and thus this study compared the response of skin fibroblasts from normal children (n = 5) and girls with TS (n = 8) to GH, IGF-I, or a combination, by assessing the IGF binding protein (IGFBP) profile of conditioned medium harvested over 7 d. The two cell types had a comparable IGFBP profile; IGFBP-3 and IGFBP-4 were the most abundant species. TS fibroblasts produced more IGFBP-3 (d 7, 51.4 ± 45 ng/mL versus 20 ± 22 ng/mL; p < 0.05) than control cells; levels of IGFBP-4 were similar (21 ± 12 ng/mL versus 30 ± 21 ng/mL). GH did not influence IGFBP production. IGF-I treatment did not affect IGFBP-4 levels but enhanced the production of IGFBP-3 by both cell types (p < 0.05). However, the response of TS fibroblasts to IGF-I was approximately half that observed in normal cells (p < 0.05). Altered IGF-I activity, because of reduced bioavailability and/or reduced sensitivity, could contribute to the need for high GH doses in TS and for the poor response to GH in some girls with TS.
authors: Maternal and Fetal Health Research Centre, University of Manchester, St Mary's Hospital, Manchester M13 9WL, United Kingdom. melissa.westwood@manchester.ac.uk
authors: Melissa
authors: M
authors: Westwood
authors: Shahin H
authors: SH
authors: Tajbakhsh
authors: Kirk W
authors: KW
authors: Siddals
authors: Andrew J
authors: AJ
authors: Whatmore
authors: Peter E
authors: PE
authors: Clayton
mesh_terms: D000704:Analysis of Variance; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism; D010766:Phosphorylation; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014424:Turner Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C515497:IGFBP3 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C507924:JAK2 protein, human; D053614:Janus Kinase 2