Estrogen promotes luteolysis by redistributing prostaglandin F2α receptors within primate luteal cells.
Estrogen promotes luteolysis by redistributing prostaglandin F2α receptors within primate luteal cells.
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DOI：
10.1530/rep-14-0412
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Duffy DM
中科院分区：
文献类型：
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作者：
Kim SO;Markosyan N;Pepe GJ;Duffy DM
前列腺素 F2α (PGF2α) 已被提议作为灵长类动物的功能性木黄素溶血素。然而，体内施用 PGF2α 或前列腺素合成抑制剂都会引发黄体溶解。这些矛盾的发现可能反映了 PGF2α 受体 (PTGFR) 的变化或黄体寿命期间关键点对 PGF2α 的反应。目前的研究使用来自雌性食蟹猴的卵巢细胞和组织以及来自接受卵泡抽吸的健康女性的黄素化颗粒细胞来解决这个问题。 PTGFR 存在于猴颗粒细胞的细胞质中，而 PTGFR 在黄体期中后期定位于大型颗粒源性猴黄体细胞的核周区域。 PTGFR激动剂减少黄体中后期和晚期黄体细胞产生的黄体酮，但不减少来自年轻黄体的颗粒或黄体细胞产生的黄体酮。这些发现与核周 PTGFR 在功能性黄体溶解中的作用一致。使用体外维持的人黄体化颗粒细胞作为黄体细胞分化的模型来探索这一概念。在这些细胞中，PTGFR 以雌激素和雌激素受体依赖性方式从细胞质转移到核周区域。与我们对猴黄体细胞的研究结果相似，具有核周 PTGFR 的人黄体化颗粒细胞对 PTGFR 激动剂做出反应，导致黄体酮产生减少。这些数据支持这样的概念：仅当 PTGFR 位于核周区域时，PTGFR 刺激才会促进功能性黄体溶解。雌激素受体介导的 PTGFR 在黄体细胞内的重新定位可能是灵长类动物黄体溶解启动的必要步骤。
Prostaglandin F2α (PGF2α) has been proposed as a functional luteolysin in primates. However, administration of PGF2α or prostaglandin synthesis inhibitors in vivo both initiate luteolysis. These contradictory findings may reflect changes in PGF2α receptors (PTGFR) or responsiveness to PGF2α at a critical point during the life span of the corpus luteum. The current study addressed this question using ovarian cells and tissues from female cynomolgus monkeys and luteinizing granulosa cells from healthy women undergoing follicle aspiration. PTGFRs were present in the cytoplasm of monkey granulosa cells, while PTGFRs were localized to the perinuclear region of large, granulosa-derived monkey luteal cells by mid-late luteal phase. A PTGFR agonist decreased progesterone production by luteal cells obtained at mid-late and late luteal phases but did not decrease progesterone production by granulosa or luteal cells from younger corpora lutea. These findings are consistent with a role for perinuclear PTGFRs in functional luteolysis. This concept was explored using human luteinizing granulosa cells maintained in vitro as a model for luteal cell differentiation. In these cells, PTGFRs relocated from the cytoplasm to the perinuclear area in an estrogen- and estrogen receptor-dependent manner. Similar to our findings with monkey luteal cells, human luteinizing granulosa cells with perinuclear PTGFRs responded to a PTGFR agonist with decreased progesterone production. These data support the concept that PTGFR stimulation promotes functional luteolysis only when PTGFRs are located in the perinuclear region. Estrogen receptor-mediated relocation of PTGFRs within luteal cells may be a necessary step in the initiation of luteolysis in primates.