IGF-I DOES NOT MEDIATE T-LYMPHOBLAST COLONY PROLIFERATION IN RESPONSE TO STEROID AND THYROID HORMONES: STUDIES IN CONTROL AND PYGMY T-CELL LINES.• 518

The mechanism by which steroid hormones {estradiol [E₂], testosterone [T], and 1,25(OH)₂ Vitamin D₃[1,25(OH)₂D₃]} and thyroid hormones [triiodothyronine(T₃)] promote tissue growth is unknown, although, for E₂ (acting on bone and uterus) and T₃ (acting on bone), a role for local IGF-I has been suggested. We previously showed that HTLV-II-transformed T-cell lines from healthy adults augmented basal colony formation in response to peptide(GH, PTH, and ACTH) and glycoprotein (TSH) hormones through stimulation of local IGF-I. T-cell lines from African Efe Pygmies, however, were resistant to the direct and indirect growth-promoting actions of IGF-I. We, therefore, used these cell lines to determine the mechanism of T-cell growth in response to steroid and thyroid hormones. We quantified colony formation of American control T-cell lines (n=7) in the presence and absence of αIR-3 antibody against the type 1 IGF receptor and Pygmy T-cell lines (n=8) in response to E₂ (36.7-1835 pmol/L), T (34.7-17,350 pmol/L), 1,25(OH)₂D₃ (2.4-24,000 pmol/L), and T₃ (1536-192,000 pmol/L). There were no statistically significant differences by ANOVA in overall response curves for any of the four hormones comparing control clonal responses in the presence or absence of αIR-3, and no statistically significant difference in overall responses between control and Pygmy T-cell lines. From these data, we conclude that: (1) normal T-cell lines grow in response to E₂, T, 1,25(OH)₂D₃, and T₃; (2) these responses are not mediated through local IGF-I since they are unaffected by pretreatment with antibody against the type 1 IGF receptor; and (3) Pygmy T-cell lines, which are genetically resistant to IGF-I, grow equivalently to control T-cell lines in response to E₂, T, 1,25(OH)₂D₃, and T₃, further underscoring the IGF-I independence of this stimulation in our system. These findings, combined with our previous observations, indicate that T-cell growth in response to certain hormones that bind to cell-surface receptors is mediated by local IGF-I, whereas specific steroid and thyroid hormones that bind to cytoplasmic/nuclear receptors act by an IGF-I-independent mechanism.