The corpus luteum (CL)2 is a transient endocrine gland derived from an ovulated follicle within the ovary. The steroidogenic cells of the CL produce progesterone, a prerequisite for normal maintenance of pregnancy in mammals. In the event of pregnancy, the CL retains its role in progesterone synthesis in support of early pregnancy. In the absence of pregnancy luteolysis or corpus luteum regression occurs, a physiologic process associated with a reduction in progesterone secretion (functional regression) followed by death of endothelial and steroidogenic cells (structural regression) (1-4). Prostaglandin F2␣ (PGF2␣) was identified as a luteolytic factor over 35 years ago (5, 6). Recent genetic studies in mice lacking the PGF2␣ receptor (FP) further highlight the role for PGF2␣ in CL regression. Mice lacking FP receptors experience defects in CL regression and consequently parturition does not occur because of the maintenance of progesterone secretion at the end of pregnancy (7).The FP receptor is a member of the large class of heterotrimeric G-protein-coupled receptors (GPCRs) (8) and is present on the surface of steroidogenic luteal cells. PGF2␣ binding to its G q -coupled receptor results in activation of phospholipase  (PLC) and consequent generation of the second messengers; diacylglycerol and inositol trisphosphate (9). The resultant increase in protein kinase C (PKC) activity in luteal cells contributes to the activation of other downstream protein kinases. PGF2␣ stimulates the activity of the extracellular signal-regulated kinase (Erk) family of mitogen-activated protein kinases (MAPK) through a mechanism that involves the PKC-dependent phosphorylation and activation of Raf (10, 11). These events result in the induction of early response genes that code for transcription factors that in turn, alter the synthesis of proteins that regulate progesterone synthesis (12-14). Little is understood regarding other signaling mechanisms initiated by PGF2␣ that account for the actions of PGF2␣ in the CL.The mammalian target of rapamycin (mTOR) protein is a key regulator of protein translation via mechanisms involving the phosphorylation of the translation regulator eukaryotic initiation factor 4E (eIF4E) -binding protein (4EBP1) and the 70-kDa ribosomal protein S6 protein kinase 1 (S6K1) (15,16 receptor; GPCR, G-protein-coupled receptor; mTOR, mammalian target of rapamycin; m 7 G, 7-methyl-guanosine; PI3K, phosphatidylinositol-3-kinase; PGF2␣, prostaglandin F2␣; S6K1, p70 ribosomal S6 kinase; TSC2, tuberous sclerosis complex 2; FBS, fetal bovine serum; FCS, fetal calf serum; JNK, c-Jun N-terminal kinase; PMA, phorbol 12-myristate 13-acetate; PKC, protein kinase C.