IGF-I DOES NOT MEDIATE T-LYMPHOBLAST COLONY FORMATION IN RESPONSE TO ESTRADIOL, TESTOSTERONE, 1,25(OH)(2) VITAMIN-D-3, AND TRIIODOTHYRONINE- STUDIES IN CONTROL AND PYGMY T-CELL LINES

The mechanism by which estradiol, testosterone, 1,25(OH)(2) vitamin D- 3, and triiodothyronine promote tissue growth is unknown, although, in some tissues, a role for local IGF-I has been suggested. We previousl y showed that HTLV-II-transformed T-cell lines from healthy adults aug mented basal colony formation in response to peptide (growth hormone, parathormone, and adrenocorticotrophin) and glycoprotein (thyroid-stim ulating hormone) hormones through stimulation of local IGF-I. T-cell L ines hom African Efe Pygmies, however, were resistant to the direct gr owth-promoting action of IGF-I, as well as to the growth-promoting act ion of growth hormone, parathormone, adrenocorticotrophin, and thyroid -stimulating hormone. We, therefore, used these cell Lines to determin e the mechanism of T-cell growth in response to steroid and thyroid ho rmones. We quantified colony formation of American control T-cell line s in the presence and absence of alpha IR-3 antibody against the type 1 IGF receptor and Pygmy T-cell lines in response to estradiol (36.7-1 835 pmol/Liter), testosterone (397-17,350 pmol/liter), 1,25(OH)(2) vit amin D-3 (2.4-24,000 pmol/liter), and triiodothyronine (1536-192,000 p mol/liter). There were no statistically significant differences by ANO VA in overall response curves for any of the four hormones comparing c ontrol clonal responses in the presence or absence of alpha IR-3 and n o statistically significant difference in overall responsiveness betwe en control and Pygmy T-cell lines. From these data, we conclude that ( i) normal T-cell Lines grow in response to estradiol, testosterone, 1, 25(OH)(2) vitamin D-3, and triiodothyronine; (ii) these responses are not mediated through local IGF-I since they are not blocked by pretrea tment with antibody to the type 1 IGF receptor; and (iii) Pygmy T-cell lines, which are genetically resistant to IGF-I, grow equivalently to control T-cell lines in response to estradiol, testosterone, 1,25(OH) (2) vitamin D-3, and triiodothyronine, further underscoring the IGF-I independence of this stimulation in our system. (C) 1996 Academic Pres s, Inc.