Growth inhibition of the androgen responsive DDT(1)MF-2 cell line by glucocorticoids: the role of ornithine decarboxylase.

Overview

While testosterone (T) stimulates the growth of DDT(1)MF-2 cells, glucocorticoids arrest the growth of these cells in the G(0)/G(1) stage of the cycle. Ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the polyamine biosynthetic pathway, is highly sensitive both to growth and inhibitory stimuli. To assess the mechanism of glucocorticoid inhibition of cell growth, the effect of triamcinolone acetonide (TA) on growth and ODC was studied. DDT(1)-MF-2 cell growth was inhibited by TA and difluoromethyl ornithine (DFMO), an irreversible inhibitor of ODC. TA (10NM: ) inhibited the ODC activity to 10% of the control levels by 12 h and inhibition was maintained at all later intervals studied. Ten μM: DFMO inhibited ODC activity to a maximum of 50% of control. The concentration of ODC mRNA was maximally decreased at 15 h after TA administration.Though TA and DFMO inhibited cell growth and ODC activity in DDT(1)-MF2 cells, growth inhibition by DFMO, but not by TA, was overcome by the addition of putrescine, the product of ODC reaction. Thus, inhibition of ODC is one pathway through which glucocorticoids inhibit DDT(1)MF-2 cell growth. ODC inhibition, however, is not the only pathway through which glucocorticoids act.