Table I.
Enzymes and transporters in PGE2 synthesis, metabolism and transport.
| Category | Gene name | Common name | Function | Other comments |
|---|---|---|---|---|
| Phospholipase A2 | PLA2G4A | cPLA2 | Cleavage of arachidonic acid from membrane phospholipids | Calcium promotes translocation from cytosol to intracellular membranes; predominates in granulosa cells |
| PLA2G2A | sPLA2IIA | Cleavage of arachidonic acid from membrane phospholipids | Can be activated by cPLA2 | |
| PLA2G5 | sPLA2V | Cleavage of arachidonic acid from membrane phospholipids | Can be activated by cPLA2 | |
| Cyclooxygenase; prostaglandin G/H synthase | PTGS1 | COX1 | Converts arachidonic acid to PGH2 | Constitutive expression |
| PTGS2 | COX2 | Converts arachidonic acid to PGH2 | Inducible expression; predominates in granulosa cells | |
| PTGS1 | COX3, COX1b | Converts arachidonic acid to PGH2 | Splice variant of COX1; may lack enzymatic activity | |
| Prostaglandin E synthase | PTGES | mPGES1 | Converts PGH2 to PGE2 | Associated with intracellular membranes; predominates in granulosa cells |
| PTGES2 | mPGES2 | Converts PGH2 to PGE2 | Associated with intracellular membranes | |
| PTGES3 | cPGES | Converts PGH2 to PGE2 | Cytosolic enzyme | |
| Aldo Keto reductases | AKR1C1 | 20α-HSD | Converts PGE2 to PGF2α | Minimal PGE-F isomerase activity in granulosa cells; significant 20α-HSD activity |
| AKR1C2 | PGE-F isomerase, 9-keto reductase | Converts PGE2 to PGF2α | Primary PGE-F isomerase activity in granulosa cells | |
| AKR1C3 | PGFS | Converts PGH2 to PGF2α | Primary PGF2α synthase in granulosa cells | |
| Prostaglandin dehydrogenase | HPGD | PGDH | Converts many prostaglandins to 15-keto metabolites | Prostaglandin inactivation |
| Prostaglandin transporters | SLCO2A1 | PGT, OATP | Facilitates prostaglandin movement across plasma membrane | Direction of prostaglandin movement is cell dependent |
| ABCC4 | MRP4 | Facilitates prostaglandin movement across plasma membrane | Prostaglandin movement out of cells predominates |
cPLA2, cytosolic phospholipase A2; sPLA2IIA, secreted phospholipase A2 group 2A; sPLA2V, secreted phospholipase A2 group 5; COX1, cyclooxygenase 1; PGH2, prostaglandin H2; COX2, cyclooxygenase 2; COX2, cyclooxygenase 3; COX1b, cyclooxygenase 1b; mPGES1, microsomal prostaglandin E synthase 1; PGE2, prostaglandin E2; mPGES2, microsomal prostaglandin E synthase 2; cPGES, cytosolic prostaglandin E synthase; 20α-HSD, 20α-hydroxysteroid dehydrogenase; PGF2α, prostaglandin F2α; PGE-F, conversion of prostaglandins of the E series to prostaglandins of the F series; PGFS, prostaglandin F synthase; PGDH, prostaglandin dehydrogenase; PGT, prostaglandin transporter; OATP, organic anion transporting polypeptide; MRP4, multiple drug resistance protein 4.