The first product of phospholipid N-methylation, phosphatidylmonomethylethanolamine, is a lipid mediator for progesterone action at the amphibian oocyte plasma membrane.

Progesterone has been shown to act at plasma membrane receptors on the amphibian oocyte to trigger a cascade of changes in membrane phospholipids and to initiate the G(2)/M transition of the first meiotic division. The earliest event (0-1 min) is the transient N-methylation of phosphatidylethanolamine (PE) to form phosphatidylmonomethylethanolamine (PME), demonstrated using [(3)H]glycerol to prelabel oocyte plasma membrane PE. [(3)H]Glycerol-labeled PME rises 10-fold within the 1-2 min after exposure to progesterone and accounts for conversion of about 50% of the [3H]Glycerol-labeled PE. [(3)H]PME levels slowly decline over the following 10-30 min. [(3)H] or [(14)C] labeled fatty acid experiments showed that newly formed PME is enriched in linoleic or palmitic, but not in arachidonic acid, indicating that specific PE pools undergo progesterone-induced N-methylation. Two plasma membrane changes: activation of serine protease, and Ca(2+) release from the oocyte surface coincide with PME formation; both are prevented by pretreatment of oocytes with the N-methylation inhibitor, 2-methylaminoethane. Media containing PME micelles release both protease and Ca(2+) from intact oocytes within the first 1-2 min. The immediate downstream metabolites of PME, PDE and PC, do not induce serine protease activity or Ca(2+) release. We conclude that progesterone initially activates N-methyltransferase in the oocyte plasma membrane, and that the first product, PME, is responsible for activation of serine protease in the plasma membrane and the release of Ca(2+) from the oocyte surface.