Geffner M E, Bersch N, Scott M, Bailey R C, Golde D W
Department of Pediatrics, University of California at Los Angeles 90095-1752, USA.
Biochem Mol Med. 1996 Oct;59(1):72-9. doi: 10.1006/bmme.1996.0068.
The mechanism by which estradiol, testosterone, 1,25(OH)2 vitamin D3, and triiodothyronine promote tissue growth is unknown, although, in some tissues, 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 (growth hormone, parathormone, and adrenocorticotrophin) and glycoprotein (thyroid-stimulating hormone) hormones through stimulation of local IGF-I. T-cell lines from African Efe Pygmies, however, were resistant to the direct growth-promoting action of IGF-I, as well as to the growth-promoting action of growth hormone, parathormone, adrenocorticotrophin, and thyroid-stimulating hormone. 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 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 (36.7-1835 pmol/ liter), testosterone (34.7-17,350 pmol/liter), 1,25(OH)2 vitamin D3 (2.4-24,000 pmol/liter), and triiodothyronine (1536-192,000 pmol/liter). 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 alpha IR-3 and no statistically significant difference in overall responsiveness between 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 D3, and triiodothyronine; (ii) these responses are not mediated through local IGF-I since they are not blocked by pretreatment 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 D3, and triiodothyronine, further underscoring the IGF-I independence of this stimulation in our system.
雌二醇、睾酮、1,25(OH)₂维生素D₃和三碘甲状腺原氨酸促进组织生长的机制尚不清楚，尽管在某些组织中，已有人提出局部胰岛素样生长因子-I（IGF-I）发挥了作用。我们先前表明，来自健康成年人的人嗜T淋巴细胞病毒II型（HTLV-II）转化的T细胞系，通过刺激局部IGF-I，增强了对肽类（生长激素、甲状旁腺激素和促肾上腺皮质激素）和糖蛋白（促甲状腺激素）激素的基础集落形成。然而，来自非洲埃菲侏儒的T细胞系对IGF-I的直接促生长作用以及生长激素、甲状旁腺激素、促肾上腺皮质激素和促甲状腺激素的促生长作用具有抗性。因此，我们利用这些细胞系来确定T细胞对类固醇和甲状腺激素作出反应的生长机制。我们对美国对照T细胞系在存在和不存在针对1型IGF受体的α IR-3抗体的情况下的集落形成进行了定量，以及对侏儒T细胞系在雌二醇（36.7 - 1835 pmol/升）、睾酮（34.7 - 17350 pmol/升）、1,25(OH)₂维生素D₃（2.4 - 24000 pmol/升）和三碘甲状腺原氨酸（1536 - 192000 pmol/升）刺激下的集落形成进行了定量。通过方差分析（ANOVA），比较在存在或不存在α IR-3的情况下对照克隆反应，这四种激素中任何一种的总体反应曲线均无统计学显著差异，并且对照和侏儒T细胞系之间的总体反应性也无统计学显著差异。从这些数据中，我们得出结论：（i）正常T细胞系对雌二醇、睾酮、1,25(OH)₂维生素D₃和三碘甲状腺原氨酸有反应而生长；（ii）这些反应不是通过局部IGF-I介导的，因为它们不会被用针对1型IGF受体的抗体预处理所阻断；（iii）对IGF-I具有遗传抗性的侏儒T细胞系，在对雌二醇、睾酮、1,25(OH)₂维生素D₃和三碘甲状腺原氨酸的反应中，与对照T细胞系生长相当，这进一步强调了在我们的系统中这种刺激不依赖IGF-I。
