Skarzynski D J, Okuda K
Laboratory of Reproductive Endocrinology, Faculty of Agriculture, Okayama University, Okayama, Japan.
Biol Reprod. 1999 Jun;60(6):1292-8. doi: 10.1095/biolreprod60.6.1292.
Prostaglandin (PG) F2alpha that is released from the uterus is essential for spontaneous luteolysis in cattle. Although PGF2alpha 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 PGF2alpha. We examined the sensitivity of bovine CL to PGF2alpha treatment in vitro and determined whether the changes in the response of CL to PGF2alpha 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 PGF2alpha. 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 PGF2alpha and PGE2 secretion (p < 0.01) from early CL. However, it stimulated PGF2alpha secretion in mid-cycle luteal cells (p < 0.001). AT reduced P4 secretion in early and mid-cycle CL (p < 0.05). Moreover, PGF2alpha 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 PGF2alpha. PGF2alpha had no influence on OT secretion, although [Ca2+]i increased (p < 0.05) in the early CL. However, the effect of PGF2alpha was augmented (p < 0.01) in cells after pretreatment with OP, AT, and INDO in comparison with the controls. In mid-cycle luteal cells, PGF2alpha 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 PGF2alpha action.
子宫释放的前列腺素(PG)F2α对牛的自发性黄体溶解至关重要。尽管PGF2α及其类似物被广泛用于通过诱导黄体溶解来同步发情周期,但发情周期早期的黄体(CL)对PGF2α的溶黄体作用具有抗性。我们在体外研究了牛CL对PGF2α处理的敏感性,并确定CL对PGF2α反应的变化是否依赖于孕酮(P4)、催产素(OT)和局部产生的PGs。来自发情周期早期(发情周期第4 - 5天)和周期中期CL(发情周期第8 - 12天)的牛黄体细胞在接受PGF2α刺激前12小时预先暴露于P4拮抗剂(奥那司酮:OP;10(-4) M)、OT拮抗剂(阿托西班:AT;10(-6) M)或吲哚美辛(INDO;10(-4) M)。尽管OP仅在早期CL中降低了P4分泌(p < 0.001),但它降低了所检测的两个阶段细胞中的OT分泌(p < 0.001)。OP还降低了早期CL中PGF2α和PGE2的分泌(p < 0.01)。然而,它刺激了周期中期黄体细胞中PGF2α的分泌(p < 0.001)。AT降低了早期和周期中期CL中的P4分泌(p < 0.05)。此外,AT在早期CL中抑制了PGF2α的分泌(p < 0.05)。测量OT分泌和细胞内游离Ca2+([Ca2+]i)水平作为CL对PGF2α敏感性的指标。PGF2α对OT分泌没有影响,尽管早期CL中[Ca2+]i增加(p < 0.05)。然而,与对照相比,在用OP、AT和INDO预处理后的细胞中,PGF2α的作用增强(p < 0.01)。在周期中期黄体细胞中,PGF2α诱导OT分泌和[Ca2+]i增加2倍。然而,与早期CL的结果相反,这些增加仅在细胞预先暴露于AT后被放大(p < 0.05)。这些结果表明,黄体P4、OT和PGs是牛发情周期早期到中期CL中自分泌/旁分泌正反馈级联的组成部分,可能是早期牛CL对外源性PGF2α作用具有抗性的原因。