Effect of antimicrotubule agents on microtubules and steroidogenesis in luteal cells.

This report represents an effort to reinvestigate the relationship of steroid hormone processing with microtubule protein, using the highly active progesterone-producing cells of superovulated immature rats as a model steroid hormone system. For the most part, gonadotropin-primed rats were used at 6 days and were reinjected with saline or various doses of colchicine and vinblastine: after 3 h the animals were injected with human chorionic gonadotropin (hCG, 10 IU) or saline for an additional hour. Subsequently, the ovaries were perfused with fixative for morphological studies or luteal cells were isolated for in vitro incubation with various additives. The results are as follows: 1) luteal cell progesterone synthesis is reduced in a dose- and time-dependent manner after treatment with antimicrotubule drugs; 2) additional stimulating agents given in vitro (hCG, Bt2cAMP, epinephrine) do not overcome the reduction produced by treatment with antimicrotubule drugs; 3) luteal cells show normal protein synthesis after treatment with antimicrotubule drugs; 4) luteal cells have microtubules of unusual appearance that are insensitive to the action of antimicrotubule agents. These results show that in the luteinized ovary, both colchicine and vinblastine interfere with hormone-stimulated steroidogenesis. Although the mechanism for the effect is not yet understood, it does not appear to be related to the content of the intact microtubules in luteal cells. Whether the drugs exert their action by binding to the unassembled form of microtubule protein in the cells remains to be determined.