Insulin-like growth factors (IGF-I and IGF-II) and IGF-binding protein-3 production by fibroblasts of patients with Turner's syndrome in culture.
Reports indicate that in plasma insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) are normal in patients with Turner's syndrome (TS). The aim of our study was to evaluate both the spontaneous and the stimulated synthesis of these peptides by mesenchymal cells obtained from skin biopsies of patients affected with TS. We compared the ability of fibroblasts from six TS patients with that of fibroblasts from six age-matched control (C) subjects to synthesize in vitro IGF-I, IGF-II, and IGFBP-3 under basal and GH-, estradiol (E2)-, or GH- plus E2-stimulated conditions. Furthermore, we evaluated IGF-I, IGF-II, and IGFBP-3 messenger ribonucleic acid (mRNA) expression in fibroblasts from TS and C subjects. Fibroblasts obtained from TS patients release into the medium significantly lower amounts of IGF-I and IGF-II than C fibroblasts (P = 0.0435 and 0.0318, respectively). In TS fibroblasts, GH and E2 are able to induce a similar increase, although not significant, of IGF-I secretion into the medium (163 +/- 75% and 112 +/- 41% of control values). On the contrary, in C fibroblasts, GH is more effective (275 +/- 61%; P = 0.0277) than E2 (75 +/- 46%). In both cell lines, GH and E2 do not significantly modify IGF-II release. Interestingly, the medium conditioned by fibroblasts from TS contains, under basal conditions, significantly higher amounts (273 +/- 79 ng/1 x 10(6) cells) of IGFBP-3 than that from control fibroblasts (67 +/- 19 ng/1 x 10(6) cells; P = 0.0191). GH exerts a stimulatory effect, although it is not statistically significant, on IGFBP-3 secretion, particularly in control fibroblasts. By contrast, the effect of E2 is inhibitory in all TS fibroblast cell lines, although it does not reach statistical significance (P = 0.067). In agreement with these data, a reduced mRNA expression of the genes encoding for IGF peptides was evident in TS fibroblasts, whereas no significant difference could be demonstrated for IGFBP-3 mRNA. The results suggest a reduced autocrine/paracrine action of IGFs in TS and indicate that skin fibroblast cultures can give information on the local responsiveness to the treatment.
Barreca
A
A
Department of Endocrinology and Metabolism, University of Genova, Italy.
Larizza
D
D
Damonte
G
G
Arvigo
M
M
Ponzani
P
P
Cesarone
A
A
Lo Curto
F
F
Severi
F
F
Giordano
G
G
Minuto
F
F
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014424:Turner Syndrome / Q000378:metabolism* / Q000473:pathology
D004338:Drug Combinations; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II