Aouani A, Samih N, Amphoux-Fazekas T, Mezghrani A, Mykhaylov S, Hovsépian S, Lombardo D, Fayet G
INSERM - Unité 260 and Laboratoire de Biochimie Médicale, Faculté de Médecine, Marseille, France.
Horm Metab Res. 1999 Jul;31(7):402-5. doi: 10.1055/s-2007-978763.
The polar planar compound hexamethylene bisacetamide (HMBA) is an inducer of terminal differentiation which has been extensively studied in the murine erythroleukemia cells (MELC). We have tested this compound in normal porcine thyroid cells in primary culture where it either activates or inhibits the major tissue specific functions of these cells: it induces the reorganization of cells into follicles, prevents the loss of thyrotropin sensitivity in monolayer cells, activates cell growth but inhibits their iodide metabolism. In this paper, we demonstrate that HMBA acts on the total thyroglobulin levels measured in cell layers plus media. This specific marker of thyroid tissue is increased by HMBA both in kinetics and in concentration-response experiments. HMBA per se does not increase the total cyclic AMP measured either during the first hours after stimulation or in the following days when compared to controls. As expected, cyclic AMP in the same experiment increased rapidly within minutes after the cells were challenged by TSH (positive control). Altogether, the results show that the drug HMBA mimics thyrotropin effects on thyroglobulin levels measured in porcine thyroid cells in culture. This modulation cannot be explained by an increase in cyclic AMP, indicating that despite similarities between TSH and HMBA effects, the mechanism of the mode of action of these two molecules is very different.
极性平面化合物六亚甲基双乙酰胺（HMBA）是一种终末分化诱导剂，已在小鼠红白血病细胞（MELC）中得到广泛研究。我们在原代培养的正常猪甲状腺细胞中测试了这种化合物，它在这些细胞中要么激活要么抑制主要的组织特异性功能：它诱导细胞重组形成滤泡，防止单层细胞中促甲状腺素敏感性的丧失，激活细胞生长但抑制它们的碘代谢。在本文中，我们证明HMBA作用于细胞层加培养基中测得的总甲状腺球蛋白水平。在动力学实验和浓度 - 反应实验中，HMBA均使甲状腺组织的这一特异性标志物增加。与对照组相比，无论是在刺激后的最初几小时内还是在随后的几天中，HMBA本身都不会增加测得的总环磷酸腺苷（cAMP）。正如预期的那样，在同一实验中，细胞受到促甲状腺素（阳性对照）刺激后几分钟内，环磷酸腺苷迅速增加。总之，结果表明药物HMBA模拟了促甲状腺素对培养的猪甲状腺细胞中测得的甲状腺球蛋白水平的影响。这种调节不能用环磷酸腺苷的增加来解释，这表明尽管促甲状腺素和HMBA的作用存在相似性，但这两种分子的作用机制非常不同。
