Intraluteal Release of Progesterone and Prostaglandins during PGF_2α-Induced Luteolysis in Ewes: Local Effects of Tumor Necrosis Factor-α

Abstract

The role of tumor necrosis factor-α (TNF-α) in the local regulatory mechanisms of functional luteolysis in the ewe was examined. TNF-α was infused into a microdialysis system (MDS) implanted in the corpus luteum (CL) for 24 h from 2 h after the intramuscular injection of cloprostenol (defined as 0 h), and plasma as well as intraluteal changes of progesterone (P) and prostaglandins (PG) were observed. Three ewes were treated for superovulation, and multiple CL formed thereafter were surgically implanted with the MDS (1 line/CL) on Day 7 after GnRH injection. Serial fractions from the MDS were collected every 30 min for 40 h on Days 9-11 following a pre-perfusion period of 30 h. An intramuscular injection of cloprostenol stimulated an acute increase of plasma P concentration (an increase to 150%) within 1 h, followed by a rapid decrease within 6 h (P<0.05), which directly correlates with functional luteolysis. Intraluteal P release into the MDS showed a profile similar to that in the plasma, but significantly decreased from 17 h (P<0.05). Twenty-four-hour infusions of TNF-α at 20 ng/ml and 200 ng/ml into the MDS starting at 2 h after cloprostenol injection slightly hastened the time of onset of P decrease when they were compared with the time of the control. In contrast, the higher dose of TNF-α at 2000 ng/ml clearly delayed the time of onset of P decrease. Intraluteal release of PGF_2α and PGE₂ in the control was slightly increased between 18-32 h (P<0.05). A 26-h infusion with indomethacin partly blocked the increase in basal release of both PG (P<0.05), whereas it had no effect on the P release. A 24-h infusion with different concentrations of TNF-α stimulated the release of PGE₂, but not the release of PGF_2α (P<0.05). The results support the idea that TNF-α may have a passive or secondary role in functional luteolysis. Furthermore, the intraluteal PG production appears to have no direct correlation with functional luteolysis.