The effects of taxol, a microtubule-stabilizing drug, on steroidogenic cells.
The effects of taxol on steroid production and microtubule polymerization were examined using Y-1 adrenocortical tumor cells, MLTC-1 Leydig tumor cells, and primary cultures of bovine adrenocortical cells. Taxol inhibited the following steroidogenic processes within the Y-1 and MLTC-1 cells: (1) hormonal increase of steroid production, (2) dibutyryl cyclic AMP-increased steroid production, and (3) hormone-stimulated pregnenolone production. The inhibitory action of taxol was concentration dependent and also resulted in an increase in cytoplasmic microtubules. In addition, the inhibitory action of taxol on hormone-stimulated steroid production was reversible. Taxol appeared to inhibit cholesterol movement to the mitochondrial site of cholesterol side-chain cleavage enzyme but did not affect overall protein synthesis. Interestingly, taxol did not affect hormone-stimulated steroid production in bovine adrenocortical cells. This lack of inhibition may correspond to the ultrastructural observation that microtubule bundling after taxol treatment was observed in the tumor cells but not in similarly treated bovine adrenal cells. With this conflicting information between cell types, a direct relationship between taxol treatment and inhibition of steroid production has not been established. However, these results suggest that taxol alters the rate of transport of cholesterol to the cholesterol side-chain cleavage enzyme within the steroidogenic tumor cells.
Rainey
W E
WE
Kramer
R E
RE
Mason
J I
JI
Shay
J W
JW
D000302:Adrenal Cortex; D000306:Adrenal Cortex Neoplasms; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D007985:Leydig Cells; D008297:Male; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D008928:Mitochondria / Q000378:metabolism; D017239:Paclitaxel; D011284:Pregnenolone / Q000096:biosynthesis*; D011374:Progesterone / Q000096:biosynthesis*; D013256:Steroids / Q000096:biosynthesis*; D013736:Testicular Neoplasms
D000470:Alkaloids; D013256:Steroids; D011374:Progesterone; D003994:Bucladesine; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D017239:Paclitaxel