Intermediate filaments and steroidogenesis in adrenal Y-1 cells: acrylamide stimulation of steroid production.
The possible role of intermediate filaments in steroidogenesis was investigated in Y-1 mouse adrenal tumor cells by treatment with acrylamide, which is thought to disrupt intermediate filaments without directly affecting microtubules or microfilaments. Treatment of cells with 5 mM acrylamide increases steroidogenesis after a lag period of 4-6 h and induces rounding of the cells at approximately the same time. The effect of acrylamide on steroidogenesis is not cAMP mediated and occurs before pregnenolone formation. DNA synthesis is inhibited, while protein synthesis is not. Acrylamide does not affect polymerization/depolymerization of microtubules in vitro. Acrylamide stimulation of steroidogenesis is additive with that produced by either colchicine or ACTH, implying that acrylamide, ACTH, and colchicine act at different rate-limiting steps in steroidogenesis. In addition, acrylamide stimulation is additive with that of forskolin. Pretreatment of cells with taxol, an agent that specifically promotes microtubule polymerization, decreases acrylamide-stimulated (as well as colchicine or ACTH-stimulated) steroidogenesis, implying that there must also be some shared elements in the stimulating pathways. We hypothesize that regulation of steroidogenesis in the Y-1 cell depends on 1) disruption of a vimentin or tubulin coat surrounding lipid droplets and 2) possible functional shortening of the distance between cholesterol droplets and the mitochondrion. However, because of interactions between cytoplasmic fibers, it is currently impossible to say whether interruption of any one of them is a direct or indirect stimulus of steroidogenesis.
Shiver
T M
TM
National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Sackett
D L
DL
Knipling
L
L
Wolff
J
J
D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology*; D000310:Adrenal Gland Neoplasms; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D007382:Intermediate Filaments / Q000502:physiology*; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D011284:Pregnenolone / Q000096:biosynthesis; D013256:Steroids / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D000178:Acrylamides; D013256:Steroids; D020106:Acrylamide; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D004247:DNA; D000242:Cyclic AMP; D003078:Colchicine