Effects of the Protein Phosphatase Inhibitor Okadaic Acid on the Actions of Prolactin in Cultured Mouse Mammary Gland Explants

The effects of okadaic acid on ornithine decarboxylase (ODC) activity and milk product formation were studied in cultured mammary tissues derived from midpregnant mice. Okadaic acid stimulated ODC activity as well as the synthesis of lactose, lipids, and casein-rich phosphoproteins. When tested together, okadaic acid and prolactin evoked a nonadditive stimulation of lactose synthesis. In addition, the time-courses for the okadaic acid and prolactin effects on lactose synthesis were the same. In contrast to the effects of okadaic acid and prolactin on lactose synthesis, these agents generated additive stimulatory effects on ODC activity and the synthesis of lipids and casein-rich phosphoproteins. Since okadaic acid is known to inhibit protein phosphatases-1 and 2A, we conclude that the substrate(s) of these phosphatases are involved in the signal transduction pathway by which prolactin expresses its effect on lactose synthesis in mammary tissues. Whether these substrates are also involved in other actions of prolactin in mammary tissues remains to be established.