Del Terra Elisa, Francesconi Anna, Donnini Debora, Curcio Francesco, Ambesi-Impiombato Francesco Saverio
Dipartimento di Patologia e Medicina Sperimentale e Clinica and MATI Center, Università degli Studi di Udine, Udine, Italy.
Thyroid. 2003 Aug;13(8):747-53. doi: 10.1089/105072503768499635.
Apoptosis plays an important role within the endocrine system, particularly in the thyroid gland, although little is known about its regulation in normal thyroids. Because thyrotropin (TSH) regulates many thyroid-specific functions and cell proliferation, we investigated whether TSH can influence such mechanisms. To induce apoptosis we used UV-C radiation. The FRTL-5 rat thyroid cell strain, a cloned strain of differentiated and untransformed cells that reproduces many of the characteristics of the normal thyroid was chosen for this study. The FRTL-5 cells are a particularly suitable model because they actively proliferate when cultured in the presence of TSH (6H medium), while in TSH-free medium (5H medium) cells remain in a physiologic quiescent state for a long period of time. FRTL-5 cells in both culture conditions were irradiated with UV-C radiation (254 nm wavelength). At 48 hours after radiation, 6H cultured cells showed the characteristic signs of apoptosis. However, 5H cultured cells did not present macroscopic signs of damage, DNA fragmentation, or detectable apoptosis. Furthermore, the expression of 23 apoptosis-related genes was compared. Results indicate that Bcl2 and caspase-2 expression is enhanced, while bax, GADD45 and mdm-2 expression is reduced in irradiated cells. These data confirm that TSH plays a major role in regulating UV-induced apoptosis in FRTL-5 cells.
细胞凋亡在内分泌系统中发挥着重要作用,尤其是在甲状腺中,尽管目前对其在正常甲状腺中的调节机制知之甚少。由于促甲状腺激素(TSH)调节许多甲状腺特异性功能和细胞增殖,我们研究了TSH是否会影响这些机制。为了诱导细胞凋亡,我们使用了紫外线C辐射。本研究选用了FRTL-5大鼠甲状腺细胞系,这是一种分化且未转化的细胞克隆系,能再现正常甲状腺的许多特征。FRTL-5细胞是一个特别合适的模型,因为当在TSH存在的情况下培养(6H培养基)时它们会积极增殖,而在无TSH的培养基(5H培养基)中细胞会在很长一段时间内保持生理静止状态。处于这两种培养条件下的FRTL-5细胞都用紫外线C辐射(波长254nm)进行照射。辐射后48小时,在6H培养基中培养的细胞出现了细胞凋亡的特征性迹象。然而,在5H培养基中培养的细胞没有出现明显的损伤迹象、DNA片段化或可检测到的细胞凋亡。此外,还比较了23个与细胞凋亡相关基因的表达。结果表明,在受照射的细胞中,Bcl2和caspase-2的表达增强,而bax、GADD45和mdm-2的表达降低。这些数据证实,TSH在调节FRTL-5细胞中紫外线诱导的细胞凋亡方面发挥着主要作用。