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

Turner's syndrome is characterized, amongst other things, by growth retardation with high serum levels of insulin-like growth factor I (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 I-125-labelled LDL (25 mu g 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 (AMLR) and on interleukin 2 (IL-2) secretion by blastoid T-cell culture. 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 revealed a significant augmentation by 100 ng mL(-1) GH and by 50-100 ng ng mL(-1) IGF(-1) in control subjects, and almost no response in Turner's 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.