AJP - Cell Physiology, Vol 246, Issue 3 293-C300, Copyright © 1984 by American Physiological Society
Role of polyamines in differentiation of 3T3-L1 fibroblasts into adipocytes
B. G. Erwin, D. R. Bethell and A. E. Pegg
The role of polyamines in the differentiation of 3T3-L1 fibroblasts into
adipose cells was studied. This conversion was blocked by the addition of
alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor
of ornithine decarboxylase, which prevented a rise in spermidine content in
the differentiating cells. The inhibition of differentiation could be
overcome completely by the provision of exogenous putrescine, spermidine,
or spermine. Partial reversal could be produced by exposure to
nonphysiological homologues of the natural polyamines such as
1,3-diaminopropane, 1,5-diaminopentane, and sym-norspermine. Reversal of
the inhibition of differentiation by exogenous polyamines required a period
of exposure to the amines, indicating that the lack of differentiation is
not due simply to an obligatory role for polyamines in the biosynthesis of
lipids. These results indicate that spermidine is required for the
differentiation, but spermidine alone was not able to replace insulin and
1-methyl-3-isobutylxanthine in stimulating conversion to adipocytes.
Therefore spermidine appears to be necessary but not sufficient for
differentiation to occur. Finally, the elevation of spermidine content that
occurs during the conversion of fibroblasts to adipocytes did not correlate
with an increased activity of the polyamine biosynthetic enzymes. This
implies that the increase must be regulated by changes in the rate of
degradation or excretion of the polyamines.
