SYNERGISTIC EFFECTS OF PROSTAGLANDIN-F2-ALPHA AND TUMOR-NECROSIS-FACTOR TO INDUCE LUTEOLYSIS IN THE PIG

There is ample evidence that prostaglandin F-2 alpha (PGF(2 alpha)) is a luteolytic substance in sows, however, there is also some evidence that it may stimulate progesterone (P-4) secretion in young corpora lu tea (CL). In vitro studies also suggested that tumor necrosis factor a lpha (TNF) is inhibitory to luteal cell P-4 and estradiol-17 beta (E-2 ) release. Since E-2 is a strong luteotropic substance in porcine CL, we studied the effects of intraluteal application of PGF(2 alpha) and TNF alone and in combination on the secretion of P-4 and E-2 in freely moving sows. Furthermore, the effects of intraluteal infusion of E-2 and its stereoisomer, estradiol-17 alpha, on luteal function, were als o determined. Microdialysis systems were implanted into CL at Day 10 o f the estrous cycle. After a 24-h recovery period, PGF(2 alpha) (10(-6 ) M) Or E-2 (10(-6) M) was applied daily for 6 h into the CL. PGF(2 al pha) caused a stimulation of E-2 and P-4, and E-2 also stimulated P-4 secretion at Days 11 and 12, but the stimulatory effect of both substa nces diminished as the CL approached luteolysis. Intraluteal TNF appli cation resulted in a transient increase of P-4 secretion, which was fo llowed by a dramatic reduction of P, release. When TNF-pretreated CL w ere exposed to PGF(2 alpha) at Day 11 of the estrous cycle, the prosta glandin was no longer able to stimulate but rather inhibited E-2 and P -4 secretion. Intraluteal application of estradiol-17 alpha had no eff ect on P-4 secretion. These results are suggestive that the PGF(2 alph a)-induced E-2 secretion in young and middle-aged CL is stimulatory to P-4 secretion. Under the influence of macrophage-derived TNF producti on, E-2 secretion is inhibited, and thereby PGF(2 alpha) and TNF cause functional luteolysis.