Synergistic effects of prostaglandin F2alpha and tumor necrosis factor to induce luteolysis in the pig.
There is ample evidence that prostaglandin F2alpha (PGF2alpha) is a luteolytic substance in sows, however, there is also some evidence that it may stimulate progesterone (P4) secretion in young corpora lutea (CL). In vitro studies also suggested that tumor necrosis factor alpha (TNF) is inhibitory to luteal cell P4 and estradiol-17beta (E2) release. Since E2 is a strong luteotropic substance in porcine CL, we studied the effects of intraluteal application of PGF2alpha and TNF alone and in combination on the secretion of P4 and E2 in freely moving sows. Furthermore, the effects of intraluteal infusion of E2 and its stereoisomer, estradiol-17alpha, on luteal function, were also determined. Microdialysis systems were implanted into CL at Day 10 of the estrous cycle. After a 24-h recovery period, PGF2alpha (10(-6) M) or E2 (10(-6) M) was applied daily for 6 h into the CL. PGF2alpha caused a stimulation of E2 and P4, and E2 also stimulated P4 secretion at Days 11 and 12, but the stimulatory effect of both substances diminished as the CL approached luteolysis. Intraluteal TNF application resulted in a transient increase of P4 secretion, which was followed by a dramatic reduction of P4 release. When TNF-pretreated CL were exposed to PGF2alpha at Day 11 of the estrous cycle, the prostaglandin was no longer able to stimulate but rather inhibited E2 and P4 secretion. Intraluteal application of estradiol-17alpha had no effect on P4 secretion. These results are suggestive that the PGF2alpha-induced E2 secretion in young and middle-aged CL is stimulatory to P4 secretion. Under the influence of macrophage-derived TNF production, E2 secretion is inhibited, and thereby PGF2alpha and TNF cause functional luteolysis.
Wuttke
W
W
Department of Obstetrics and Gynecology, University of Göttingen, Germany. ufkendo@med.uni-goettingen.de
Spiess
S
S
Knoke
I
I
Pitzel
L
L
Leonhardt
S
S
Jarry
H
H
D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology*; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008186:Luteolytic Agents / Q000494:pharmacology*; D017551:Microdialysis; D011247:Pregnancy; D013552:Swine; D013556:Swine, Miniature; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D008186:Luteolytic Agents; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D015237:Dinoprost