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This Article Full Text Full Text (PDF) All Versions of this Article: 76/4/619    most recent biolreprod.106.053280v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Skarzynski, D. J. Articles by Okuda, K. Search for Related Content PubMed PubMed Citation Articles by Skarzynski, D. J. Articles by Okuda, K. Agricola Articles by Skarzynski, D. J. Articles by Okuda, K.

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 Inhibitor¹

Department of Reproductive Immunology,³ Institute of Animal Reproduction and Food Research, PAS, Olsztyn 10-747, Poland Department of Pathology and Pharmacology,⁴ Faculty of Veterinary Medicine, Warmia and Mazury University in Olsztyn, Olsztyn 10-975, Poland Laboratory of Reproductive Endocrinology,⁵ Graduate School of Natural Sciences and Technology, Okayama University, Okayama 700-8530, Japan

ABSTRACT

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 µg 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 µg) in combination with INDO or L-NAME. TNF at 1 µg 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 PGE₂ 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 µg) infused into the uterine lumen prolonged the CL lifespan, low doses (0.01 and 0.1 µg) 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. PGE₂ is a good candidate mediator of the luteotropic actions of exogenous TNF action.

corpus luteum function, cytokine, estrus cycle, necrosis factor, ovulatory cycle, progesterone, prostaglandins, tumor, uterus

¹Supported by the Grants-in-Aid for Scientific Research from the Polish Ministry of Sciences and Informative Technology (2 P06K 025 29) and the Japan Society for Promotion of Sciences (JSPS; 18658114). D.J.S. was supported under the JSPS Invitation Fellowship Program for Research in Japan for Senior Scientists. I.W.-P. was supported by the Domestic Grants for Young Scientists of the Foundation for Polish Science (FNP Programme 2006).

Correspondence: ²FAX: 48 89 535 74 38; e-mail: skadar{at}pan.olsztyn.pl

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