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a Trigger for the Initiation of Endometrial Prostaglandin F2 Release at Luteolysis in Cattle?1
a Laboratory of Reproductive Endocrinology, Faculty of Agriculture, Okayama University, Okayama 700–8530, Japan
To determine the physiological significance of tumor necrosis factor 
(TNF) in the regulation of luteolytic prostaglandin (PG) F2 release by the bovine endometrium, the effect of TNF- on PGF2 output by the endometrial tissues in vitro was investigated and compared with the effect of oxytocin (OT). Furthermore, the presence of specific receptors for TNF in the bovine endometrium during the estrous cycle was determined. Endometrial slices (20–30 mg) taken from six stages of the estrous cycle (estrus: Day 0; early I: Days 2–3; early II: Days 5–6; mid-: Days 8–12; late: Days 15–17; and follicular: Days 19–21), as determined by macroscopic examination of the ovaries and uterus, were exposed to TNF (0.06–6 nM) and/or OT (100 nM). OT stimulated PGF2 output at the follicular stage and at estrus (P < 0.001), but not at the late luteal stage. On the other hand, the stimulatory effects of TNF on PGF2 output were observed not only at the follicular stage but also at the late luteal stage (P < 0.001). When the endometrial tissues at late luteal stage were simultaneously exposed to TNF (0.6 nM) and OT (100 nM), the stimulatory effect on PGF2 output was higher than the effect of TNF or OT alone (P < 0.05). Specific binding of TNF to the bovine endometrial membranes was observed throughout the estrous cycle. The concentration of TNF- receptor at the early I luteal stage was less than the concentrations at other luteal stages (P < 0.01). The dissociation constant (Kd) values of the endometrial membranes were constant during the estrous cycle. The overall results lead us to hypothesize that TNF may be a trigger for the output of PGF2 by the endometrium at the initiation of luteolysis in cattle.
1 This research was supported by Grants-in-Aid for Scientific Research (No. 11556054 and 11460129) and a Research Fellow (No. 07809) of the Japan Society for the Promotion of Science (JSPS) from the Ministry of Education, Science, Sports and Culture of Japan. D.J.S. was a postdoctoral fellow supported by JSPS.
2 Correspondence: Kiyoshi Okuda, Laboratory of Reproductive Endocrinology, Division of Animal Science and Technology, Faculty of Agriculture, Okayama University, Okayama 700–8530, Japan. FAX: 81 86 251 8388; kokuda{at}cc.okayama-u.ac.jp
3 Current address: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10–718 Olsztyn-Kortowo, Poland.
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