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Lithium ion at concentrations between 2 and 20 mM simulated the stimulatory effects of insulin on the uptake of alpha-aminoisobutyric acid, synthesis of RNA and DNA, and cell multiplication in mouse mammary gland explants cultured in a chemically defined synthetic medium. Other monovalent cations were virtually ineffective. In most instances the stimulatory effect of lithium ion was somewhat smaller than and additive to that of insulin. However, lithium ion was incapable of substituting for the action of insulin in augmenting milk protein synthesis in mammary explants cultured with other lactogenic hormones, prolactin, and glucocorticoid. The observed similarities of the responses of mammary cells to lithium and insulin suggest that possible importance of cation(s) in the regulation of mammary cell proliferation, which may be a common basis for the action of the two agents. On the other hand, the observed inability of lithium to mimic the lactogenic effect of insulin indicates a specific function of the hormone in the functional differentiation of mammary cells.

Induction by lithium ion of multiplication of mouse mammary epithelium in culture.