Spermidine is necessary for, but not the only mediator of, linoleic acid-stimulated alpha-casein accumulation in mouse mammary epithelial cells.

Mammary epithelial cells obtained from virgin mice were induced to accumulate alpha-casein in serum-free two-stage collagen gel culture with insulin, PRL, and linoleic acid. Omission of either PRL or linoleic acid drastically reduces alpha-casein accumulation. Spermidine addition to insulin-containing medium in either the absence or presence of linoleic acid does not stimulate alpha-casein accumulation. We conclude from this that spermidine can not be the sole mediator of PRL action. Spermidine also will not replace linoleic acid for alpha-casein accumulation if the fatty acid is omitted from the culture medium and will not increase casein accumulation when supplemented into PRL- and linoleic acid-containing medium; thus, it is not the sole mediator of linoleic acid action. However, the spermidine synthesis inhibitor methylglyoxal-(bis)-guanylhydrazone does inhibit alpha-casein accumulation in a concentration-dependent and spermidine-recoverable manner in cells stimulated by PRL and linoleic acid. We could not detect changes in polyamine levels in response to any of the medium supplements used in this investigation. Spermidine is, thus, at least a required comediator of the alpha-casein synthesis induction, although its role remains enigmatic.