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.
Teaff
N L
NL
Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan.
Savoy-Moore
R T
RT
Subramanian
M G
MG
Ataya
K M
KM
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011374:Progesterone / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013480:Superovulation / Q000187:drug effects; D014747:Vinblastine / Q000494:pharmacology*
D011458:Prostaglandins E; D011374:Progesterone; D014747:Vinblastine