Sensitivity of bovine corpora lutea to prostaglandin F(2α) is dependent on progesterone, oxytocin, and prostaglandins

Prostaglandin (PG) F(2α) that is released from the uterus is essential for spontaneous luteolysis in cattle. Although PGF(2α) 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 PGF(2α). We examined the sensitivity of bovine CL to PGF(2α) treatment in vitro and determined whether the changes in the response of CL to PGF(2α) 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 PGF(2α). 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 PGF(2α) and PGE₂ secretion (p < 0.01) from early CL. However, it stimulated PGF(2α) secretion in mid-cycle luteal cells (p < 0.001). AT reduced P₄ secretion in early and mid-cycle CL (p < 0.05). Moreover, PGF(2α) 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 PGF(2α). PGF(2α) had no influence on OT secretion, although [Ca²⁺](i) increased (p < 0.05) in the early CL. However, the effect of PGF(2α) was augmented (p < 0.01) in cells after pretreatment with OP, AT, and INDO in comparison with the controls. In mid-cycle luteal cells, PGF(2α) 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 PGF(2α) action.