Stimulation of steroid secretion by antimicrotubular agents.

The antimicrotubular agents colchicine, vinblastine, and podophyllotoxin have been found to stimulate steroid production by Y-l adrenal tumor cells in culture. The amount of steroid secreted under the influence of these agents is comparable to the amount produced during maximal adrenocorticotropin (ACTH) stimulation. The steroid end products, ZOa-dihydroprogesterone and llfl-hydroxy-20a-dihydroprogesterone, are identical after both kinds of stimulation. ACTH stimulation and vinblastine stimulation are not additive. As with ACTH, stimulation by vinblastine occurs between the cholesterol and A4-pregnenolone steps, and it is inhibited by aminoglutethimide and cycloheximide. It does not, however, involve activation of the adenylate cyclase system. The time course of stimulation differs from ACTHthe antimicrotubular agents stimulate after a 6to 9-hour lag period which is absent with ACTH. D20, an agent which stabilizes microtubules, inhibits stimulation of steroid by vinblastine, ACTH, or cyclic adenosine 3’,5’-monophosphate (CAMP). Steroid secretion by Leydig tumor cells in culture is also stimulated by vinblastine, but to a lesser extent than by CAMP. This stimulation exhibits a lag period and is inhibited by DpO. We propose that the antimicrotubular agents facilitate access of cholesterol to the mitochondrion and that this may also be the mechanism of hormonally-stimulated steroid secretion.