In Vitro Studies on the Nature of Vinblastine Inhibition of Thyroid Secretion
- 1 June 1976
- journal article
- research article
- Published by The Endocrine Society in Endocrinology
- Vol. 98 (6) , 1351-1358
- https://doi.org/10.1210/endo-98-6-1351
Abstract
The effects of vinblastine on thyroid secretion were studied in mouse thyroid glands in vitro. Inhibition of the secretory response to TSH [thyrotropin] was observed within the first 30 min of exposure to vinblastine and was largely complete after 1 h. Inhibition of colloid droplet formation and hormonal radioiodine release was comparable for both TSH and cyclic AMP stimulation. No reversal of inhibition was seen when thyroids exposed to vinblastine were subsequently washed 2 or 4 h in vinblastine free medium, nor could previous vinblastine inhibition be overcome by high levels of TSH or dibutyryl cyclic AMP. Ultrastructural effects of vinblastine (1 .times. 10-5 M) were studied under conditions similar to those used to demonstrate inhibition of secretion. Microtubules present in thyroids incubated in control medium were reduced after 30 min and almost completely abolished after 1 or 2 h exposure to vinblastine. No other reproducible structural changes were seen. A higher concentration of vinblastine (5 .times. 10-5 M) produced lysosomal clumping and the formation of numerous vinblastine crystalloids. Uptake and washout of [3H]-vinblastine were studied with both phases showing fast and slow components. The initial uptake phase (T1/2 [half-life] .apprx. 12 min) correlates well with the disappearance of microtubules and the inhibition of thyroid secretion. A prolonged washout component (T1/2 = 10-18 h) may account for the irreversibility of vinblastine inhibition of in vitro thyroid secretion. Inhibition of thyroid secretion produced by vinblastine is consistent with its actions on thyroidal microtubules.This publication has 1 reference indexed in Scilit:
- Membrane-bound tubulin in brain and thyroid tissue.Journal of Biological Chemistry, 1975