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* Department of Pharmacology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland;
Division of Reproductive Endocrinology and Pathophysiology, Institute of Animal Reproduction and Food Research, Polish Academy of Science, Olsztyn 10-747 Olsztyn, Poland;
Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157; and
Department of Reproductive Biotechnology, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808
The objective of the present study was to investigate the role of cell-to-cell contact in the influence of nitric oxide (NO) on the secretory function of the bovine corpus luteum (CL). In Experiment 1, separate small luteal cells (SLC) or large (LLC) luteal cells were perfused with 100 µM spermineNONOate, a NO donor, or with 100 µM N
-nitro-L-arginine methyl ester (L-NAME), a NO synthase (NOS) inhibitor; in Experiment 2, a mixture of LLC and SLC and endothelial cells was cultured and incubated with spermineNONOate or L-NAME; in Experiment 3, spermineNONOate was perfused into the CL (100 mg/4 hr) by a microdialysis system in vivo. Perfusion of isolated SLC and LLC with the NO donor or NOS inhibitor (Experiment 1) did not affect (P > 0.05) secretion of progesterone (P4) or oxytocin (OT). L-NAME perfusion increased (P < 0.05) leukotriene C4 (LTC4) secretion by both SLC and LLC cells. Treatment of mixtures of luteal cells with an NO donor (Experiment 2) significantly decreased (P < 0.001) secretion of P4 and OT and increased (P < 0.001) production of prostaglandin F2
(PGF2
) and LTC4. L-NAME stimulated (P < 0.001) P4 secretion, but did not influence (P > 0.05) OT, PGF2
or LTC4 production. Intraluteal administration (Experiment 3) of spermineNONOate increased (P < 0.001) LTC4 and PGF2
, decreased OT, but did not change P4 levels in perfusate samples. These data indicate that cell-to-cell contact and cell composition play important roles in the response of bovine CL to treatment with NO donors or NOS inhibitors, and that paracrine mechanisms are required for the full secretory response of the CL in NO action. Endothelial cells appear to be required for the full secretory response of the CL to NO.
Key Words: nitric oxide progesterone oxytocin prostaglandin F2
leukotriene C4 bovine
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