Colchicine-binding protein and the secretion of thyroid hormone.
The role of microtubules in the thyrotropin- or adenosine 3',5' cyclic monophosphate (cyclic AMP)-stimulated accumulation of cytoplasmic colloid droplets and secretion of iodine from the mouse thyroid gland has been investigated by means of different classes of agents that affect the stability of microtubules. The onset of inhibition of secretion by colchicine, the uptake of colchicine-(3)H by thyroid lobes, and the binding of colchicine-(3)H to thyroidal soluble protein are shown to have similar time courses Colloid droplet accumulation is also inhibited and does not readily resume upon removal of colchicine from the medium. This appears to be due to the slow washout of the drug (t((1/2)) approximately hr). Thyroids contain a soluble colchicine-binding protein that resembles microtubule proteins of other tissues with respect to apparent K(m) for colchicine, pH optimum, and stability characteristics Colchicine analogues inhibit iodine secretion and colchicine binding in a parallel manner and as a function of their antimitotic potencies. Microtubule-stabilizing agents such as hexylene glycol and D(2)O also inhibit secretion. Thus, inhibition of thyroid secretion by antimitotic agents appears to be mediated by an effect on microtubules. The inhibitory locus of colchicine inhibition occurs after the generation of cyclic AMP, since stimulation of secretion by this nucleotide is blocked by colchicine, whereas thyroid-stimulating hormone-induced accumulation of cyclic AMP is not affected. Thus, the functioning microtubule appears to play a role in the induction of colloid endocytosis.
D000818:Animals; D003078:Colchicine / Q000378:metabolism / Q000494:pharmacology*; D003102:Colloids; D000242:Cyclic AMP / Q000032:analysis / Q000494:pharmacology; D003903:Deuterium / Q000494:pharmacology; D006018:Glycols / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007455:Iodine / Q000378:metabolism*; D007456:Iodine Isotopes; D008722:Methods; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium
D003102:Colloids; D006018:Glycols; D007456:Iodine Isotopes; D014316:Tritium; D013972:Thyrotropin; D007455:Iodine; D003903:Deuterium; D000242:Cyclic AMP; D003078:Colchicine