Insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins (IGFBPs) were examined in Ishikawa endometrial cancer cells. Our findings suggest that about 95% of [125I]IGF-I is bound to membrane-associated IGFBPs rather than to IGF-I receptors. Specifically, [125I]IGF-I binding to cell membranes could be completely displaced by cold IGF-I or IGF-II, but not by insulin, suggesting that binding was primarily due to IGFBPs. This was confirmed by using [125I]des-(1-3)IGF-I as the ligand. Des-(1-3) IGF-I binds with high affinity to IGF-I receptors, but with markedly lower affinity to IGFBPs. [125I]Des-(1-3)IGF-I bound to Ishikawa cells was displaced by IGF-I, IGF-II, and insulin. These results suggest that measuring IGF-I receptor levels using labeled IGF-I may be misleading. Accordingly, we evaluated the differential binding of [125I]IGF-I and [125I]des-(1-3)IGF-I to study the involvement of the IGF system in the stimulation of Ishikawa cell growth by estradiol. IGF-I stimulates Ishikawa cell proliferation, but at low concentrations, and this stimulation is largely dependent on the presence of estradiol. Estradiol caused a 2.5-fold increase in IGF-I receptor levels. Moreover, estradiol reduced soluble IGFBP levels, presumably increasing the availability of IGFs for their receptors. This elevation in IGF-I receptor levels and the decrease in IGFBP levels were accompanied by a 3.5-fold increase in IGF-I receptor messenger RNA and a 2.5-fold decrease in IGFBP messenger RNAs. These experiments suggest that estradiol sensitizes endometrial cancer cells to the effects of IGFs by simultaneously elevating receptor levels and decreasing (potentially inhibitory) IGFBP levels.
The feasibility of applying elevated Chlamydia trachomatis specific IgG antibody and serum IgA antibodies as a non-invasive screening test for C. trachomatis associated salpingitis was analysed in 54 salpingitis patients and 294 apparently healthy women by the single antigen (L2) immunoperoxidase assay (IPA). The prevalence rate of C. trachomatis IgG antibody (titre greater than or equal to 64) was significantly higher in the salpingitis patients in comparison to control (67% versus 23%). The prevalence rate of elevated C. trachomatis IgG titres (greater than or equal to 128, greater than or equal to 256 and greater than or equal to 512) was significantly higher in the salpingitis patients as compared to the controls. For example, at an IgG titre of greater than or equal to 128 the prevalence rate was 57% in the salpingitis patients and 8% in the healthy controls (p less than 0.0001). The prevalence of C. trachomatis IgA antibodies (titre greater than or equal to 16) was significantly higher in salpingitis patients in comparison to controls (37% versus 4%). The prevalence of elevated IgA titres (greater than or equal to 32 and greater than or equal to 64) was found to be significantly higher in salpingitis patients as compared to controls. All the IgG seropositive salpingitis patients were also found to have C. trachomatis IgG antibodies. It appears that testing for IgG antibodies at a serum dilution of 1:128, and for IgA antibodies at a dilution of 1:16 by the IPA test comprises the best combination for the differentiation between the salpingitis patients and apparently healthy controls, and it is suggested that this be used as a marker of active C. trachomatis infection.
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