Prostaglandin synthases: recent developments and a novel hypothesis.
Cells are continuously exposed to cues, which signal cell survival or death. Fine-tuning of these conflicting signals is essential for tissue development and homeostasis, and defective pathways are linked to many disease processes, especially cancer. It is well established that prostaglandins (PGs), as signalling molecules, are important regulators of cell proliferation, differentiation and apoptosis. PG production has been a focus of many researchers interested in the mechanisms of parturition. Previously, investigators have focussed on the committed step of PG biosynthesis, the conversion by prostaglandin H synthase (PGHS; also termed cyclo-oxygenase, COX) of arachidonic acid (AA) (substrate) to PGH2, the common precursor for biosynthesis of the various prostanoids. However, recently the genes encoding the terminal synthase enzymes involved in converting PGH2 to each of the bioactive PGs, including the major uterotonic PGs, PGE2 (PGE synthase) and PGF2alpha (PGF synthase), have been cloned and characterized. This review highlights how the regulation of the expression and balance of key enzymes can produce, from a single precursor, prostanoids with varied and often opposing effects.
Helliwell
Rachel J A
RJ
Department of Anatomy with Radiology, Faculty of Medicine and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand. r.helliwell@auckland.ac.nz
Adams
Linda F
LF
Mitchell
Murray D
MD
D016718:Arachidonic Acid / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000235:genetics / Q000378:metabolism
D007527:Isoenzymes; D011453:Prostaglandins; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase; D015232:Dinoprostone