Effect of decreasing intraluteal progesterone on sensitivity of the early porcine corpus luteum to the luteolytic actions of prostaglandin F2alpha.
Effect of decreasing intraluteal progesterone on sensitivity of the early porcine corpus luteum to the luteolytic actions of prostaglandin F2alpha.
复制标题
减少黄体酮对早期猪黄体对前列腺素 F2α 黄体溶解作用敏感性的影响。
DOI：
10.1095/biolreprod.110.084368
复制
发表时间：
2011
影响因子：
3.6
通讯作者：
Wiltbank,MiloC
中科院分区：
文献类型：
--
作者：
Diaz,FranciscoJ;Luo,Wenxiang;Wiltbank,MiloC
前列腺素F2 α（PGF）仅在发情周期第12天后引起猪黄体（CL）的黄体溶解。最近的证据表明，孕酮（P4）可以保护CL免于细胞死亡。本研究验证了以下假设：在缺乏黄体溶解能力的CL（第9天CL）中，通过用依泊坦（EPO; 3 β HSD抑制剂）治疗对P4的急性抑制将允许PGF诱导与黄体溶解相关的反应。评价了多种PGF诱导的反应，包括参与PGF和雌二醇-17 β产生、细胞凋亡（半胱天冬酶3）和转录（FOSB）的基因。这些反应与PGF诱导的黄体溶解有关，通常不会发生在缺乏黄体溶解能力的CL中。发情后第7天的动物分为4组：1）对照组（C）、2）PGF组、3）EPO组和4）PGF + EPO组（PGF+EPO）。每12 h给予EPO（10 mg/kg）或溶媒治疗，持续36 h。在38 h时给予PGF（25 mg）或溶剂处理，并在48 h时收集所有动物的CL。将来自每只动物的一些CL冷冻在液氮中用于mRNA和蛋白质分析。将剩余的CL在培养基中孵育2小时以测定P4和PGF的产生。EPO和PGF+EPO组与C组相比，显著降低黄体组织P4的产生（ng/mg组织），分别为90%和95%（P< 0.01）。在C、PGF和EPO组中，发现黄体组织产生PGF较低;然而，用PGF+EPO治疗显著增加黄体PGF产生（782%）。与输卵管内PGF产生相似，在PGF+EPO组中发现环氧化酶2（PTGS 2）和磷脂酶A2（组IB; PLA 2G 1B）的mRNA增加，但在EPO或PGF组中没有。PGF和EPO对芳香化酶（CYP 19 A1）mRNA无诱导作用;而PGF+EPO使CYP 19 A1 mRNA表达增加40倍以上CASP 3 mRNA表达增加（P< 0.01），促红细胞生成素（EPO）组与对照组比较，差异有显著性（P< 0.01）（3.4倍）和PGF（2.7倍），但通过PGF+EPO（5.3倍）最显著地增加，而胱天蛋白酶活性仅通过PGF（1.5倍）或PGF+EPO（2.2倍）增加。因此，这些数据支持这一假设，即消除黄体内P4的保护作用并不直接导致早期CL的黄体溶解，但允许PGF诱导缺乏黄体溶解能力的CL的黄体溶解反应。
Prostaglandin F2alpha (PGF) causes luteolysis of the pig corpus luteum (CL) only after Day 12 of the estrous cycle. Recent evidence indicates that progesterone (P4) may protect the CL from cell death. The present study tested the hypothesis that acute inhibition of P4 by treatment with epostane (EPO; 3betaHSD inhibitor) in CL lacking luteolytic capacity (Day 9 CL) will allow PGF to induce responses associated with luteolysis. Multiple PGF-induced responses were evaluated, including genes involved in production of PGF and estradiol-17beta, apoptosis (caspase 3), and transcription (FOSB). These responses are associated with PGF-induced luteolysis and do not normally occur in CL lacking luteolytic capacity. Animals on Day 7 after estrus were divided into four groups: 1) control (C), 2) PGF, 3) EPO, and 4) PGF plus EPO (PGF+EPO). Treatment with EPO (10 mg/kg) or vehicle was given every 12 h for 36 h. Treatment with PGF (25 mg) or vehicle was given at 38 h, and CL were collected from all animals at 48 h. Some CL from each animal were frozen in liquid nitrogen for mRNA and protein analysis. Remaining CL were incubated in media for 2 h for determination of P4 and PGF production. EPO dramatically decreased production of P4 by luteal tissue (ng/mg tissue) by 90% and 95% in EPO and PGF+EPO groups, respectively, compared to C (P< 0.01). Low production of PGF by luteal tissue was found in C, PGF, and EPO groups; however, treatment with PGF+EPO dramatically increased (782%) luteal PGF production. Similar to intraluteal PGF production, increased mRNA for cyclooxygenase 2 (PTGS2) and phospholipase A2 (group IB;PLA2G1B) was found in the PGF+EPO, but not in the EPO or PGF, group. Aromatase (CYP19A1) mRNA was not induced by PGF or EPO; however, PGF+EPO caused a more than 40-fold increase inCYP19A1mRNA (P< 0.01).CASP3mRNA was increased (P< 0.01) by EPO (3.4-fold) and by PGF (2.7-fold) but was most dramatically increased by PGF+EPO (5.3-fold), whereas caspase activity was only increased by PGF (1.5-fold) or PGF+EPO (2.2-fold). Thus, these data support the hypothesis that elimination of the protective effect of intraluteal P4 does not directly cause luteolysis of the early CL but allows PGF to induce luteolytic responses in CL lacking luteolytic capacity.