Infusion of exogenous tumor necrosis factor dose dependently alters the length of the luteal phase in cattle: differential responses to treatment with indomethacin and L-NAME, a nitric oxide synthase inhibitor.
We examined whether prostaglandins (PGs) and nitric oxide (NO) mediate tumor necrosis factor (TNF) actions in the estrus cycle. On Day 14 of the cycle, the following solutions were infused into the aorta abdominalis of a total of 51 heifers (Experiments 1 and 2): saline; 1 or 10 microg of TNF; 480 mg indomethacin (INDO), an inhibitor of prostaglandin H synthase; 800 mg L-NAME, an inhibitor of NO synthase; and TNF (1 or 10 microg) in combination with INDO or L-NAME. TNF at 1 microg infused directly into aorta abdominalis increased the level of PGF(2alpha) and decreased the level of progesterone (P4) in the peripheral blood and shortened the estrus cycle. The high TNF dose stimulated P4 and PGE(2) and prolonged the corpus luteum (CL) lifespan. INDO blocked the effects of both TNF doses on the CL lifespan and hormone output. L-NAME completely blocked the effects of the luteolytic TNF dose, whereas the effects of the luteotropic TNF dose were not inhibited. In Experiment 3 (Day 14), saline or different TNF doses were infused into the jugular vein (n = 9) or into the uterine lumen (n = 18). The CL lifespans of the different groups were not different when TNF was infused into the jugular vein. Although high TNF doses (1 and 10 microg) infused into the uterine lumen prolonged the CL lifespan, low doses (0.01 and 0.1 microg) induced premature luteolysis. We suggest that the actions of exogenous TNF on the CL lifespan depend on PG synthesis stimulated by TNF in the uterus. TNF at low concentrations initiates a positive cascade between uterine PGF(2alpha) and various luteolytic factors, including NO, to complete premature luteolysis. PGE(2) is a good candidate mediator of the luteotropic actions of exogenous TNF action.
Skarzynski
Dariusz J
DJ
Department of Reproductive Immunology, Institute of Animal Reproduction and Food Research, PAS, Olsztyn 10-747, Poland. skadar@pan.olsztyn.pl
Woclawek-Potocka
Izabela
I
Korzekwa
Anna
A
Bah
Mamadou M
MM
Piotrowska
Katarzyna
K
Barszczewska
Beata
B
Okuda
Kiyoshi
K
D000818:Animals; D002417:Cattle / Q000097:blood / Q000502:physiology; D003338:Corpus Luteum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D007260:Infusion Pumps; D008183:Luteal Phase / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011374:Progesterone / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D014599:Uterus / Q000098:blood supply / Q000187:drug effects
D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin