Abstract

Phospholipase A2 and arachidonic acid mimic the stimulatory effect of prolactin on casein exocytosis. We suggest that prolactin by activating phospholipase A2, induces a release of arachidonic acid which is metabolized by a cyclooxygenase pathway leading to prostaglandins, prostacyclins and thromboxanes, a lipoxygenase pathway leading to hydroperoxides and leukotrienes and an epoxygenase pathway. The effects of prolactin and of the major products of arachidonic acid metabolism were studied by incubating mammary gland fragments of lactating rabbit and by measuring neosynthesized caseins and prostaglandins F (PGF2 alpha) in the incubation medium. Aspirin (10(-3) M) which strongly decreases PGF2 alpha synthesis did not modify exocytosis or prolactin stimulation of exocytosis. However, in some cases where prolactin did not stimulate exocytosis, aspirin could restore this stimulation. Nor-dihydroguaiaretic acid (10 microM), an inhibitor of lipoxygenases, increased PGF2 alpha synthesis in the presence of prolactin. In parallel, this inhibitor increased casein exocytosis but inhibited prolactin stimulation. These results are consistent with the action of arachidonic acid metabolites in the regulation of casein exocytosis. We suggest a dual control by the metabolites of the lipoxygenase and the cyclooxygenase pathways.

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