Effects of microtubule inhibitors and cytochalasin B on thyroid metabolism in vitro.
Mitotic spindle inhibitors (colchicine, vinblastine, vincristine, 020, ethanol) and cytochalasin B inhibit the phagocytosis of colloid by thyroid cells and the secretion of thyroid hormones. This inhibition has been linked to interferences with the microtubular microfilament system of the follicular cell. In order to test the possibility of using such inhibitors to selectively block secretion, the action of suppressing or highly inhibitory concentrations on other metabolic parameters has been studied on dog thyroid slices in vitro: glucose oxidation, lactate formation, iodide binding to protein, cyclic 3'5' AMP accumulation. It is shown that at a concentration of 10 mM colchicine is entirely non specific as it greatly inhibits all facets of metabolism and all the stimulatory effects of cyclic 3'5' AMP and thyrotropin. The other mictrotubule inhibitors, although affecting thyroid metabolism in various ways were more specified. The enhancement by vineblastine of glucose oxidation ald iodine binding to proteins suggests an activation of they thyroid H2O2 generating system. D2O on the other hand selectively inhibits secretion and the binding of iodide to proteins. Cytochalasin B, presumably by inhibiting hexose transport, decreased glycolysis and the uptake of iodide. However this effect cannot account for the complete inhibition of thyroid secretion.
D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology*; D003903:Deuterium / Q000494:pharmacology; D004285:Dogs; D000431:Ethanol / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007454:Iodides / Q000378:metabolism; D007773:Lactates / Q000096:biosynthesis; D008870:Microtubules / Q000187:drug effects*; D010084:Oxidation-Reduction; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D007454:Iodides; D007773:Lactates; D011506:Proteins; D003571:Cytochalasin B; D000431:Ethanol; D014750:Vincristine; D014747:Vinblastine; D013972:Thyrotropin; D003903:Deuterium; D000242:Cyclic AMP; D005947:Glucose; D003078:Colchicine