title: The first product of phospholipid N-methylation, phosphatidylmonomethylethanolamine, is a lipid mediator for progesterone action at the amphibian oocyte plasma membrane.
abstract: 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.
authors.affiliation: Department of Physiology & Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Kostellow
authors.forename: G Y
authors.initials: GY
authors.lastname: Ma
authors.forename: G A
authors.initials: GA
authors.lastname: Morrill
mesh_terms: D000818:Animals; D002118:Calcium / Q000819:agonists / Q000493:pharmacokinetics; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D004789:Enzyme Activation / Q000187:drug effects; D004980:Ethane / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D008540:Meiosis / Q000187:drug effects; D008745:Methylation; D009865:Oocytes / Q000378:metabolism*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D011894:Rana pipiens; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010714:Phosphatidylethanolamines; D010743:Phospholipids; C032000:phosphatidyl-N-monomethylaminoethanol; D011374:Progesterone; D010664:Phenylmethylsulfonyl Fluoride; D012697:Serine Endopeptidases; D004980:Ethane; D002118:Calcium