Vinblastine reduces progesterone and prostaglandin E production by rat granulosa cells in vitro.
To elucidate the possible mechanism(s) of vinblastine-induced premature ovarian failure, we studied the effect of vinblastine (VLB) on progesterone (P) and prostaglandin E (PGE) production by rat granulosa cells in vitro. Granulosa cells obtained from immature, pregnant mares' serum gonadotrophin-primed rats were incubated for 5 h in modified Medium 199 +/- LH (10 ng/mL) with varying concentrations of VLB (0.001 to 10.0 micrograms/mL) and cells plus media were assayed for total P and PGE. VLB reduced production of both basal and LH-stimulated P in granulosa cells, with VLB at a concentration of 0.1 micrograms/mL showing the first significant difference from control. This dose also suppressed basal and LH-stimulated PGE. Granulosa cell survival was similar for all groups. Thus VLB, an agent known to disrupt microtubular function, reduced granulosa cell production of both P and PGE. Our results suggest that at a concentration (0.1 micrograms/mL) lower than that routinely achieved during chemotherapy (0.3 micrograms/mL), VLB depresses rat granulosa cell function in vitro. This system appears to be a valid model for preliminary assessment of the cytotoxic effects of chemotherapy on an ovarian component.[1]References
- Vinblastine reduces progesterone and prostaglandin E production by rat granulosa cells in vitro. Teaff, N.L., Savoy-Moore, R.T., Subramanian, M.G., Ataya, K.M. Reprod. Toxicol. (1990) [Pubmed]
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