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Sensitivity of Bovine Corpora Lutea to Prostaglandin F₂ Is Dependent on Progesterone, Oxytocin, and Prostaglandins¹

^a Laboratory of Reproductive Endocrinology, Faculty of Agriculture, Okayama University, Okayama 700–8530, Japan

Prostaglandin (PG) F₂ that is released from the uterus is essential for spontaneous luteolysis in cattle. Although PGF₂ and its analogues are extensively used to synchronize the estrous cycle by inducing luteolysis, corpora lutea (CL) at the early stage of the estrous cycle are resistant to the luteolytic effect of PGF₂. We examined the sensitivity of bovine CL to PGF₂ treatment in vitro and determined whether the changes in the response of CL to PGF₂ are dependent on progesterone (P₄), oxytocin (OT), and PGs produced locally. Bovine luteal cells from early (Days 4–5 of the estrous cycle) and mid-cycle CL (Days 8–12 of the estrous cycle) were preexposed for 12 h to a P₄ antagonist (onapristone: OP; 10^-4 M), an OT antagonist (atosiban: AT; 10^-6 M), or indomethacin (INDO; 10^-4 M) before stimulation with PGF₂. Although OP reduced P₄ secretion (p < 0.001) only in early CL, it reduced OT secretion in the cells of both phases examined (p < 0.001). OP also reduced PGF₂ and PGE₂ secretion (p < 0.01) from early CL. However, it stimulated PGF₂ secretion in mid-cycle luteal cells (p < 0.001). AT reduced P₄ secretion in early and mid-cycle CL (p < 0.05). Moreover, PGF₂ secretion was inhibited (p < 0.05) by AT in early CL. The OT secretion and the intracellular level of free Ca²⁺ ([Ca²⁺]_i) were measured as indicators of CL sensitivity to PGF₂. PGF₂ had no influence on OT secretion, although [Ca²⁺]_i increased (p < 0.05) in the early CL. However, the effect of PGF₂ was augmented (p < 0.01) in cells after pretreatment with OP, AT, and INDO in comparison with the controls. In mid-cycle luteal cells, PGF₂ induced 2-fold increases in OT secretion and [Ca²⁺]_i. However, in contrast to results in early CL, these increases were magnified only by preexposure of the cells to AT (p < 0.05). These results indicate that luteal P₄, OT, and PGs are components of an autocrine/paracrine positive feedback cascade in bovine early to mid-cycle CL and may be responsible for the resistance of the early bovine CL to the exogenous PGF₂ action.

¹ This research was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (No. 96346), by the Polish National Research Council (Grant KBN 5 P06K 027 13), by the Japanese-German Cooperative Science Promotion Program of the Japanese Society for the Promotion of Science (JSPS), and by a grant for the specific research "The study of the development of organisms effective to environmental conservation for human life" at Okayama University. D.J.S. is a postdoctoral fellow supported by JSPS.

² Correspondence. FAX: 81 86 251 8388; kokuda{at}cc.okayama-u.ac.jp

³ Permanent address: Division of Reproductive Endocrinology and Pathophysiology, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10–718 Olsztyn-Kortowo, Poland.

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