Vinblastine-Induced Inhibition of Protein Transport in the Mouse Thyroidin Vivo*

Publisher Website
Google Scholar
Abstract
Mice pretreated with propylthiouracil (for 12–14 days) and T4 (for days) were injected iv with vinblastine (Vb; 1 mg) 2–4 h before sacrifice and 1 h before radioleucine. The effect of Vb on thyroid morphology and protein transport was studied with quantitative electron microscopy, cell fractionation, and electron microscopic autoradiography. Vb caused the disappearance of microtubules and the appearance of typical paracrystals in the follicle cell cytoplasm. Cell fractionation and autoradiography showed that Vb inhibited the transfer of newly synthesized protein to the follicle lumen. This inhibition appeared to be partly due to a diminished formation of exocytotic vesicles, almost exclusively present in the supranuclear region in controls, and partly due to a retarded transport of newly formed exocytotic vesicles toward the follicle lumen; after Vb treatment, labeled exocytotic vesicles were dispersed in all parts of the cytoplasm, including infranuclear regions often associated with dislocated Golgi areas. This redistribution together with a reduction in their total number led to a decrease in the number of exocytotic vesicles present in the supranuclear region of the follicle cell by about 80% (2 h) and 70% (4 h). Recent observations in this laboratory suggest that experimental reduction of the pool of exocytotic vesicles in the supranuclear cell region of the follicle cell leads to a parallel reduction of the endocytotic response to TSH. This suggests the possibility that the decreased endocytotic response to TSH after Vb observed in previous studies is secondary to the decrease in the number of exocytotic vesicles in the supranuclear cell region caused by a disturbed intracellular protein transport observed in the present study. (Endocrinology106: 833, 1980)