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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.

vasodilative Thyroid diseases have been associated with pathophysiological changes in the vasculature that may result from altered thyroid hormone production or to direct effect of elevated thyrotropin (TSH) levels on smooth muscle cells. A direct effect of TSH on vascular endothelium has not been considered. In the present study a strain of human aortic endothelial cells has been stimulated with TSH, and vascular parameters correlated with the atherosclerotic process have been analyzed. Addition of TSH induced an increase of cyclic AMP (cAMP) concentration in human aortic endothelial cells. Furthermore it induced a decrease of endothelin (from 30 +/- 2.5 to 13 +/- 1 fmol/mL) and of tissue plasminogen activator secretion (from 2,800 +/- 200 to 1,600 +/- 150 ng/mL). On the other hand, it increased nitric oxide (from 148 +/- 8 to 211 +/- 12 microM). TSH did not affect plasminogen activator inhibitor 1. Similar results were obtained when immunoglobulin Gs (IgGs) from Graves' disease patients were used. In conclusion, our findings suggest that TSH and IgGs from Graves' disease patients could stimulate endothelial cells, increasing the secretion of procoagulant and vasodilative factors, and that cAMP is involved in the transduction pathway. These findings are consistent with modifications of the fibrinolytic system reported in hypothyroidism and in Graves' disease. On the other hand, the increase of vascular resistance found in patients with hypothyroidism may be due to the altered thyroid hormone production and not to TSH directly, or to a different effect of TSH on peripheral vessels.