Inhibition of the steroidogenic responses to ACTH and dibutyl cyclic AMP in Y-1 cells by four cytochalasins (E, D, B and H2B) was examined to determine whether the capacities of these agents to inhibit these responses could be related to their abilities to inhibit polymerization of actin from Y-1 cells and to their potencies in causing rounding of the same cells. Two steroidogenic responses were examined: production of 20α-dihydroprogesterone and transport of cholesterol to inner mitochondrial membrane. The relative potencies of the four cytochalasins were compared on the basis of the concentrations (ED50) required to produce half-maximal rate of rounding and those required to produce 50% inhibition of the steroidogenic responses to ACTH and bibutyl cyclic AMP and 50% inhibition of initial velocity of polymerization of Y-1 cell actin in 1 mM magnesium. The four cytochalasins were ranked in the same order of decreasing potency in all of the determinations (E>D>B>H2B). Moreover, each cytochalasin showed approximately the same ED50 for all of the determinations. From these findings approximately the same potency ratios wre observed for the different cytochalasins in these parameters, namely E>D × 10; D>B × 9.3 and B>H2B × 1.3. These findings suggest that the cytochalasins inhibit steroidogenesis and produce rounding of cells by interfering with polymerization of actin and not in as the result of effects unrelated to binding to actin. Similar results were obtained in serum-free medium. These observations lend further support to the hypothesis that the steroidogenic responses to ACTH and dibutyl cyclic AMP require microfilamants which are involved in the intracellular transport of cholesterol.
ASJC Scopus subject areas
- Molecular Biology