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

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 are...