CONVERSION OF 3T3 FIBROBLASTS INTO ADIPOSE-CELLS - TRIGGERING OF DIFFERENTIATION BY PROSTAGLANDIN-F2ALPHA AND 1-METHYL-3-ISOBUTYL XANTHINE

Green and Kehinde isolated clones of Swiss [mouse] 3T3 fibroblasts that are able to convert to adipose cells. Two chemicals are reported (prostaglandin F2.alpha. 0.1 .mu.g/ml, and 1-methyl-3-isobutyl xanthine, 0.5 mM) that are able to rapidly and irreversibly program the fibroblasts to differentiate into adipose cells. Confluent cultures treated with prostaglandin F2.alpha. and insulin for 3-5 days, followed by insulin alone for 7-48 h, yield numerous adipocyte colonies compared to control dishes and dishes treated with insulin alone. Cells treated with prostaglandin F2.alpha. or 1-methyl-3-isobutyl xanthine alone, rinsed, and then exposed to insulin gave similar results, indicating that the continuous presence of the triggering agent is not required to elicit the conversion of the fibroblasts to adipocytes. Agents that raise intracellular levels of cyclic[c]AMP (dibutyryl cAMP, 1.0 mM; 8-bromo-cAMP, 0.5 mM; and prostaglandin E1, 0.1 .mu.g/ml) do not trigger the conversion process, suggesting that cAMP may not be the mediator of differentiation in these cells. 8-Bromo-cAMP, however, does induce the cAMP phosphodiesterase (3'':5''-cyclic-nucleotide phosphodiesterase; 3'':5''-cyclic nucleotide 5''-nucleotidohydrolase; EC 3.1.4.17) in these cells; the induction appears to be mediated by increases in intracellular cAMP levels. This cell line might offer a system for studying the regulation of a type of cellular differentiation.