Decreased sensitivity to insulin‐like growth factor I in Turner's syndrome: a study of monocytes and T lymphocytes

Abstract

Turner's syndrome is characterized, amongst other things, by growth retardation with high serum levels of insulin-like growth factor 1 (IGF-I) in relation to growth, by a tendency to autoimmune disease and by insulin resistance with hyperlipidaemia. Assuming a role for IGF-I subresponsiveness in the last two features, the present study was designed to evaluate in patients with Turner's syndrome their monocyte/macrophage response to growth hormone (GH) and to IGF-I with respect to low-density lipoprotein (LDL) degradation and to the monocyte-dependent lymphocyte proliferation. Nineteen patients with Turner's syndrome and puberty-matched control subjects were studied. Monocytes were isolated from the blood of the patients and the control group, and cultured to develop into macrophages. The cells were then incubated with 125I-labelled LDL (25 micrograms of protein mL-1) in the absence or presence of 50 ng mL-1 IGF-I or GH, and cellular lipoprotein degradation was determined. GH and IGF-I effects on T-cell proliferation were measured in autologous mixed lymphocyte reaction Monocytes/macrophages degradation of LDL was lower in Turner's syndrome patients than in control subjects (P < 0.05). IGF-I stimulated LDL degradation by 42 +/- 8% in the control subjects and by only 16 +/- 7% in Turner's syndrome patients (P < 0.05). Control lymphocyte proliferation in AMLR was significantly augmented by 50-100 ng mL-1 GH or IGF-I. Lymphocytes derived from peripheral blood of Turner's syndrome patients remained almost unaffected by either GH or IGF-I. Measurement of IL-2 secretion by purified blastoid T lymphocytes-I. revealed a significant augmentation by 100 ng mL-1 GH and by 50-100 ng mL-1 IGF-I in control subjects, and almost no response in Turner's0 ng syndrome. Turner's syndrome is associated with decreased sensitivity of peripheral blood mononuclear cells to GH and to IGF-I, as is evident by the reduction in LDL degradation, monocyte-stimulated T-lymphocyte proliferation and IL-2 secretion by blastoid T cells.

Final height in young women with Turner syndrome after GH therapy: an open controlled study

“…The dose of GH required to accelerate growth in Turner syndrome is larger then that used for GH deficiency or for idiopathic short stature, suggesting some resistance along the GH-IGF-I axis. Whereas serum GH and IGF-I are generally normal in Turner syndrome, we have recently demonstrated decreased sensitivity to GH and IGF-I of lymphocytes and monocytes in patients with this syndrome (19). Nevertheless, this would account for only a small part of the mechanism underlying growth retardation in Turner syndrome, since the final height is only partly restored by GH therapy.…”

Increased spontaneous, tumor necrosis factor receptor- and CD95 (Fas)-mediated apoptosis in cord blood T-cell subsets from Turner's syndrome

“…11,[12][13][14][15][16] In the present neonate with Turner's syndrome, we have also observed decreased proportions of both CD4+ (7.6%) and CD8+ (5.2%) T cells as compared to normal cord blood CD4+ (41.9%) and CD8+ (30.8%) T cells ( Figure 1). However, the mechanism(s) of cell-mediated immune defects and T-cell lymphopenia in Turner's syndrome has not been explored.…”

“…[9][10][11][12][13][14][15][16][17] However, the mechanism(s) for the underlying immunodeficiency has not been explored.…”

Bone maturation in girls with Turner's syndrome

“…A large volume of literature has been devoted to the regulation of enchondral ossification by growth hormone (GH), insulin-like growth factor (IGF)-I and local growth factors (13). In that respect, serum GH has been reported to decrease during the adolescence of girls with Turner's syndrome (14) and recent indirect evidence has suggested that the growth retardation in Turner's syndrome may be linked to decreased sensitivity to IGF-I (15).…”