Thyrotropin effects on ultraviolet radiation-dependent apoptosis in FRTL-5 cells

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 un-transformed 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 Bcl-2 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.