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 de rived from midpregnant mice. Okadaic acid stimulated ODC activity as w ell as the synthesis of lactose, lipids, and casein-rich phosphoprotei ns. When tested together, okadaic acid and prolactin evoked a nonaddit ive stimulation of lactose synthesis. In addition, the time-courses fo r the okadaic acid and prolactin effects on lactose synthesis were the same. In contrast to the effects of okadaic acid and prolactin on lac tose synthesis, these agents generated additive stimulatory effects on ODC activity and the synthesis of lipids and casein-rich phosphoprote ins. Since okadaic acid is known to inhibit protein phosphatases-1 and 2A, we conclude that the substrate(s) of these phosphatases are invol ved in the signal transduction pathway by which prolactin expresses it s effect on lactose synthesis in mammary tissues. Whether these substr ates are also involved in other actions of prolactin in mammary tissue s remains to be established.