de Mello-Coelho V, Gagnerault M C, Souberbielle J C, Strasburger C J, Savino W, Dardenne M, Postel-Vinay M C
INSERM U-344, Endocrinologie Moleculaire, and Universite Paris V, CNRS URA 1461, Hopital Necker, Paris, France.
Endocrinology. 1998 Sep;139(9):3837-42. doi: 10.1210/endo.139.9.6199.
GH has been shown to modulate various functions of the thymus. We now demonstrate the production of human GH (hGH) by human thymic cells, and the expression of GH receptors in thymic epithelial cells (TEC) and in thymocytes at different stages of differentiation. The presence of hGH messenger RNA was shown by RT-PCR in both human thymocytes and in primary cultures of TEC. Moreover, immunoreactive hGH material was detected in culture media of thymocytes and TEC with the use of a sensitive immunoradiometric assay. GH receptor gene expression was shown in TEC in primary cultures and in fetal and postnatal TEC lines as well as in thymocytes. By immunocytochemistry, the presence of GH receptors in the various TEC preparations was confirmed. In cytofluorometric studies with the use of a biotinylated anti-GH receptor monoclonal antibody, we could show that GH receptors are predominantly expressed by immature thymocytes: over 90% of CD3- CD4- CD8- CD19- CD34+ CD2- cells (a phenotype characterizing the most immature T cell progenitors in the thymus) were GH receptor positive. Our results provide a molecular basis for an autocrine/paracrine mode of action of GH in the human thymus.
生长激素(GH)已被证明可调节胸腺的多种功能。我们现在证明人类胸腺细胞可产生人GH(hGH),并且在不同分化阶段的胸腺上皮细胞(TEC)和胸腺细胞中存在GH受体的表达。通过逆转录聚合酶链反应(RT-PCR)在人类胸腺细胞和TEC原代培养物中均显示出hGH信使核糖核酸(mRNA)的存在。此外,使用灵敏的免疫放射分析方法在胸腺细胞和TEC的培养基中检测到免疫反应性hGH物质。在原代培养的TEC、胎儿及出生后TEC系以及胸腺细胞中均显示出GH受体基因表达。通过免疫细胞化学方法证实了各种TEC制剂中存在GH受体。在使用生物素化抗GH受体单克隆抗体的细胞荧光分析研究中,我们可以表明GH受体主要由未成熟胸腺细胞表达:超过90%的CD3-CD4-CD8-CD19-CD34+CD2-细胞(一种表征胸腺中最未成熟T细胞祖细胞的表型)为GH受体阳性。我们的结果为GH在人类胸腺中的自分泌/旁分泌作用模式提供了分子基础。