Inhibition of the nuclear entry of 3,3',5'-triiodo-L-thyronine by monodansylcadaverine in GH3 cells.
We have recently reported that the entry of 3,3',5-triiodo-L-thyronine (T3) into mouse 3T3 fibroblasts occurs by receptor-mediated endocytosis (Cheng, S. Y., Maxfield, F. R., Robbins, J., Willingham, M. C., and Pastan, I. (1980) Proc. Natl. Acad. Sci. U. S. A. 77: 3425-3429). In this communication, we evaluated the functional significance of this mode of entry using GH3 cells, a growth hormone-producing cell line which has a high number of T3 nuclear receptors. T3-specific, saturable membrane uptake systems were demonstrated in GH3 cells. Monodansylcadaverine, an inhibitor of alpha 2-macroglobulin, epidermal growth factor, vesicular stomatitis virus, and T3 uptake in fibroblasts, blocked virtually all of the cellular uptake of T3, with a half-maximal concentration of 29 microM. Concomitant with the inhibition of the cellular uptake of T3, the accumulation of T3 into nuclei was reduced. The inhibitory effect of monodansylcadaverine on the reduction of T3 incorporation into nuclei was not due to the inhibition of binding to nuclear receptors, but probably was due to a decrease in the cytoplasmic availability of T3 as a result of inhibition of cellular entry. These results indicate that the uptake of T3 by receptor-mediated endocytosis is a physiologically significant process.[1]References
- Inhibition of the nuclear entry of 3,3',5'-triiodo-L-thyronine by monodansylcadaverine in GH3 cells. Horiuchi, R., Cheng, S.Y., Willingham, M., Pastan, I. J. Biol. Chem. (1982) [Pubmed]
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